Ejercicio y Genes 2020 PDF

Ejercicio
y Genes
Dr. Jorge Cancino L. PhD.

jcancino@uft.cl Avda. Pedro de Valdivia 1509
Providencia, Santiago
+56 2 2420 7100
www.finisterrae.cl
• El genoma humano tiene alrededor de 3 billones de
pares de bases nitrogenadas.
• De ese total, sólo el 5% corresponde a regiones que
“encodan”.
Codón
• Un codón es un triplete de bases nitrogenadas.
• Cada aminoácido está representado por un codón.
• Es la forma de transmisión de la información desde
el ADN al ARN.
Anticodón
• Es el equivalente a los codones, pero en el ARNt
Intrones
• Es un fragmento de ADN que está presente en un
gen pero que no codifica ningún fragmento de la
proteína. Los intrones son eliminados en el proceso
de maduración del ARN.
Exones
• Es una porción del gen que se conserva durante el
proceso de procesamiento del ARN.
• Es en los exones que se contiene la información
para la síntesis de proteínas.
Intrones y exones
miARN (MicroARN)
• Son secuencias de ARN de alrededor de 20
nucleótidos, producidos durante el proceso de
transcripción del ADN.
• Cumplen funciones reguladoras de la expresión
génica al interactuar con el ARNm.
Histonas
Los alelos
• Cada persona tiene dos copias de un mismo gen.
• Estos se denominan Alelos.
• Un sujeto puede tener una o dos copias de la
variante más frecuente (copia “normal”) o una o
dos copias de la variante menos frecuente (copia
polimórfica o mutada.
Mutación vs Polimorfismo
• Cuando una variación genética ocurre en menor del
1% de la población, se habla de mutación.
• En cambio para variaciones que ocurren en más de
1% de la población, se consideran polimorfismos.
Variabilidad genética
• Cambios en una base nitrogenada (Ej. En la secuencia
AACGGT el nucléotido G es intercambado por un nucleótido
A, siendo la secuencia variante AACAGT).
• Deleciones de una base nitrogenada (Ej. en la secuencia
AACGGT, el nucleótido G es borrado, siendo la secuencia
variante AACGT).
• Inserción de una base nitrogenada (Ej. En la secuencia
AACGGT, el nucléotido C is insertado, siendo la secuenciaa
variante AACCGGT).
• Cambios, deleciones o inserciones en dos o más pares de
bases.
El tipo de variación más común en el genoma humano consiste
en el cambio en una sóla base nitrogenada (Polimorfismo de
nucléotido simple; SNP)
Locus
Ubicación definitiva
de un gen dentro
de un cromosoma.
Locus genético
Polimorfismo de
nucléotido simple (SNP)
SNP
• Variación en la secuencia de ADN que afecta sólo a
una base.
I/D
• Se refiere a la inserción (I) o deleción (D) de una
secuencia en el gen.
• El ejemplo más estudiado es el que respecta al gen
ACE (enzima convertidora de angiotensina).
Genética y Ejercicio
Gen ACE
• El gen de ACE humano comprende 21 kb, contiene
26 exones y 25 intrones y se encuentra en el
cromosoma 17.
• El polimorfismo ACE I/D (rs # 4646994) representa
el más común y más entendido con respecto a su
asociación con la presión arterial, enfermedades
cardiovasculares y renales, respuesta de sodio en la
dieta, ejercicio, y la respuesta de la presión arterial
a la medicación.
The Association of Sport Performance with ACE and
ACTN3 Genetic Polymorphisms: A Systematic Review and
Meta-Analysis
Fang Ma1., Yu Yang2., Xiangwei Li2, Feng Zhou2, Cong Gao2, Mufei Li2, Lei Gao2*
1 The Kinesiology Laboratory, Physical Education Institute, Xinjiang Normal University, Urumqi, China, 2 MOH Key Laboratory of Systems Biology of Pathogens, Institute of
Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College,
Sport Beijing,
Performance China Genetic Polymorphisms
and Human
Abstract
Background: Genetic polymorphism is suggested to be associated with human physical performance. The angiotensin I-
converting enzyme insertion/deletion (ACE I/D) polymorphism and the a-actinin-3 gene (ACTN3) R577X polymorphism have
been most widely studied for such association analysis. However, the findings are frequently heterogeneous. We aim to
summarize the associations of ACE I/D and ACTN3 R577X with sport performance by means of meta-analysis.
Methods: We systematically reviewed and quantitatively summarized published studies, until October 31, 2012, on
relationship between ACE/ACTN3 genetic polymorphisms and sports performance, respectively.
Results: A total of 366 articles on ACE and 88 articles on ACTN3 were achieved by literature search. A significant association
was found for ACE II genotype compared to D allele carriage (DD+ID) with increased possibility of physical performance (OR,
1.23; 95% CI, 1.05–1.45). With respect to sport discipline, the II genotype was found to be associated with performance in
endurance athletes (OR, 1.35; 95% CI, 1.17–1.55). On the other hand, no significant association was observed for ACTN3 RR
genotype as compared to X allele carriage (XX+RX) (OR, 1.03; 95% CI, 0.92–1.15). However, when restricted the analyses to
power events, a significant association was observed (OR, 1.21; 95% CI, 1.03–1.42).
Conclusion: Our results provide more solid evidence for the associations between ACE II genotype and endurance events
and between ACTN3 R allele and power events. The findings suggest that the genetic profiles might influence human
physical performance.
Citation: Ma F, Yang Y, Li X, Zhou F, Gao C, et al. (2013) The Association of Sport Performance with ACE and ACTN3 Genetic Polymorphisms: A Systematic Review
and Meta-Analysis. PLoS ONE 8(1): e54685. doi:10.1371/journal.pone.0054685
Editor: German E. Gonzalez, University of Buenos Aires, Cardiovascular Pathophysiology Institute, Argentina
Received June 22, 2012; Accepted December 17, 2012; Published January 24, 2013
Copyright: ! 2013 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was supported by the New Century Excellent Talents Support Program of the Chinese Ministry of Education (NCET-01-0288). The funders
had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: gaolei@ipbcams.ac.cn
. These authors contributed equally to this work.
Introduction gene [3,4]. The ACE insertion/deletion (ACE I/D, rs1799752)

polymorphism has been related with improvements in perfor-
Elite athletes are defined as the one who has competed at a mance and exercise duration in a variety of populations. The I
national or international level in a given sport [1]. The concept allele, which represents an insertion of 287 bp, is associated with
that genetic traits are strongly associated with human physical lower serum [5] and tissue [6] ACE activity and improved
performance has been wildly accepted in the past decade. For performance in endurance sports. The deleted form of the
instance, it was suggested that the heritability of athlete status was variant (D allele) is associated with higher circulating and tissue
estimated at approximately 66% [2]. Researchers are now ACE activity [7] and enhanced performance at sports requiring
concentrating on looking for the exact genetic profiles contribute sprinting or short bursts of power. ACTN3 has also been well
to sport performance and determining the underlying mechanisms studied as a target gene. The ACTN3 gene encodes the protein a
involved in specific fields of elite athletic performance. One of the
-actinin-3, which is almost exclusively expressed to sarcomere of
main aims of such studies is to help clinicians and coaches to
the fast glycolytic type II fibers that are responsible for the
recognize
Figure 1.and
Flowguide
Diagram individuals with genetic potentiality to be elite
of study design. generation of rapid forceful contractions during activities such as
athletes.
doi:10.1371/journal.pone.0054685.g001
sprinting and weightlifting [8,9]. A genetic variation in the
Here, we specifically consider two genes which have been
ACTN3 gene that results in the replacement of an arginine (R)
extensively studied
CI, 1.17–1.55). for may
These results the suggest
association with athletic
for larger population ability,
stratified analyses of with
power aevents
stopincodon
our present
(X) study are
at amino acid 577 (R577X, rs1815739)
namely,
and more the angiotensin
specific I-converting
studies in different ethnic groups.enzyme (ACE) a- these studies as well (OR, 1.55; 95% CI, 1.21–
and with
consistent
can create two different versions of the ACTN3 gene. Both of
these two versions are common doi:10.1371/journal.pone.0054685
PLoS
actinin-3 (ACTN3).
The ACTN3 The first
gene encodes evidence
for the synthesis ofofa-actinin-3
genetic inpolymorphisms
1.98). As ACTN3 R allele was suggested to ONE 8(1):
be associated e54685.
with
in the general population.
influencing human
skeletal-muscle fibres, aphysical performance
sarcomeric protein necessary forisproduc-
reportedpower ACE
forperformance, ACTN3 XX might be postulated to contribute
ing ‘explosive’ powerful contractions. A premature stop codon to endurance performance theoretically. However, reports from
polymorphism in ACTN3 was first described by North and Asians and Africans suggested that ACTN3 deficiency might not
PLOScolleagues
ONE | [26].
www.plosone.org
In 2003, Yang et al. demonstrated a significant 1
associated with endurance performance [32,33]. January 2013 | Volume 8 | Issue 1 | e54685
ACE
• El polimorfismo ACE inserción/deleción (ACE I/D,
rs1799752) ha sido relacionado con mejoras en el
rendimiento y resistencia en una variedad de
poblaciones.
• El alelo I, el cual representa una inserción de 287 bp
(pares de bases) es asociado con menores niveles
séricos y tisulares de ACE, además de un mejor
rendimiento en deportes de duración.
• La forma deleción de la variante (Alelo D) es asociada
con mayores niveles de ACE circulantes y mayor
rendimiento en deportes que requieren sprints o
potencia.
Figure 2. Meta-analysis of the association between sport performance and ACE polymorphism (II vs. ID+DD). Abbreviation: CI,
confidence interval; OR, odds ratio. *Different study population from the same article.
discussed the important issues on methodology of such studies conducted a meta-analysis on the published association between
[36]. However, these reviews did not verify their findings by ACTN3 and athletic status up to November 29, 2010 and observed
quantitative analysis in this review. Tamuno and colleagues an overrepresentation of the ACTN3 R577X RR genotype in
PLOS ONE | www.plosone.org 4 January 2013 | Volume 8 | Issue 1 | e54685

Figure 3. Meta-analysis of the association between sport performance and ACE polymorphism (II+ID vs. DD). Abbreviation: CI,
power athletes in Europeans [35]. However, original article might introduce selection bias into the summarized results. In
reported departure of Hardy-Weinberg Equilibrium (HWE) in the addition, there are 12 articles on this topic were newly published in
control group was not excluded from this meta-analysis, which the past two years and were included in our update meta-analysis.

ACTN-3
• Variación genética que resulta en el reemplazo de
Arginina (R) con un codón de detención (X) en el
aminoácido 577 (R577X, rs1815739).
• Esto crea dos versiones diferentes del gen ACTN3
con tres polimorfismos heredables.
• RR
• RX
• XX
https://www.snpedia.com/index.php/Rs1815739
Figure 4. Meta-analysis of the association between sport performance and ACTN3 polymorphism (RR vs. RX+XX). Abbreviation: CI,
confidence interval; OR, odds ratio. *, **Different study population from the same article.
Although the major findings were not substantially changed, our of the different criterions of elite athletes. Second, because not all
results provided more solid evidence for the relationship between necessary information could be obtained from all included studies,
ACTN3 R577X genotype and sport performance. more detailed sub-analysis was limited. For example, the crude
There are some limitations of this systematic review that should division of ethnics groups into ‘Asian’, ‘African’ and ‘Western’ may
be kept in mind. First, the potential confounding effect of make the analyses be prone to bias. Therefore, further studies from
performance level was not considered in present study because different populations are warranted to verify the current findings.

Figure 5. Meta-analysis of the association between sport performance and ACTN3 polymorphism (RR+RX vs. XX). Abbreviation: CI,
Third, only articles provided data on both athletes and sedentary reporting negative genetic association are less likely to be
controls were included in this present study, which might published than others showing ‘statistical significance’ (‘positive
introduce potential selection bias. Fourth, although studies results’), no evident publication bias was observed in our present

Papadimitriou et al. BMC Genomics (2016) 17:285
DOI 10.1186/s12864-016-2462-3
RESEARCH ARTICLE Open Access
ACTN3 R577X and ACE I/D gene variants

influence performance in elite sprinters: a
multi-cohort study
Ioannis D. Papadimitriou1, Alejandro Lucia2, Yannis P. Pitsiladis3, Vladimir P. Pushkarev4, Dmitry A. Dyatlov5,
Evgeniy F. Orekhov5, Guilherme G. Artioli6, João Paulo L. F. Guilherme6, Antonio H. Lancha Jr6,
Valentina Ginevičienė7, Pawel Cieszczyk8,16, Agnieszka Maciejewska-Karlowska8, Marek Sawczuk8,
Carlos A. Muniesa9, Anastasia Kouvatsi10, Myosotis Massidda11, Carla Maria Calò11, Fleur Garton15,
Peter J. Houweling15, Guan Wang3, Krista Austin3, Anastasiya M. Druzhevskaya12, Irina V. Astratenkova13,
Ildus I. Ahmetov14, David J. Bishop1, Kathryn N. North15 and Nir Eynon1*
Abstract
Background: To date, studies investigating the association between ACTN3 R577X and ACE I/D gene variants and
elite sprint/power performance have been limited by small cohorts from mixed sport disciplines, without
quantitative measures of performance. Aim: To examine the association between these variants and sprint time in
elite athletes.
Methods: We collected a total of 555 best personal 100-, 200-, and 400-m times of 346 elite sprinters in a large
cohort of elite Caucasian or African origin sprinters from 10 different countries. Sprinters were genotyped for ACTN3
R577X and ACE ID variants.
Results: On average, male Caucasian sprinters with the ACTN3 577RR or the ACE DD genotype had faster best 200-m
sprint time than their 577XX (21.19 ± 0.53 s vs. 21.86 ± 0.54 s, p = 0.016) and ACE II (21.33 ± 0.56 vs. 21.93 ± 0.67 sec,
p = 0.004) counterparts and only one case of ACE II, and no cases of ACTN3 577XX, had a faster 200-m time than the 2012
London Olympics qualifying (vs. 12 qualified sprinters with 577RR or 577RX genotype). Caucasian sprinters with the ACE
DD genotype had faster best 400-m sprint time than their ACE II counterparts (46.94 ± 1.19 s vs. 48.50 ± 1.07 s, p = 0.003).
Using genetic models we found that the ACTN3 577R allele and ACE D allele dominant model account for 0.92 % and
1.48 % of sprint time variance, respectively.
Conclusions: Despite sprint performance relying on many gene variants and environment, the % sprint time variance
Genomic DNA was isolated from buccal epithelium, or R allele homozygotes, RX heterozygotes and homozy-
white blood cells. The Australian, Greek, Italian, Lithu- gotes for the X allele, respectively; for the R allele
anian, US, Jamaican, Russian (from St Petersburg) and dominant or X allele dominant genetic models, the
Papadimitriou
Spanish et al. BMC
sprinters’ DNA Genomics
samples (2016)
were17:285
genotyped using the corresponding values were 0, 0, 1 or 0, 1, 1,Page 3 of 8
respect-
polymerase chain reaction (PCR)-restriction fragment ively. The proportion of the genetic contribution to
length polymorphism (RFLP) method as previously de- phenotypic variance explained by each genetic model
scribed [4]. was estimated by expressing r2 from the correlation
The DNA samples of the Polish, Brazilian, Russian analyses (taken as an estimate of percentage variance
(from
Table 1Chelyabinsk),
The 100-m, 200-m wereand genotyped
400-m bestinsprint
duplicates using explained
times (average±SD) in males according
under the to ACTN3
model)R577Xas genotype distribution
a percentage of the
an allelic discrimination assay on a Step One Real- variance explained by genotype
Caucasians effects in the model-
African Ancestry
Time PCR instrument (Applied Biosystems, Carlsbad, free ANOVAs. This proportion was compared for
Running event/Genotype RR RX XX RR + DD + RX RR RX
California, USA) with Taqman® probes. To discri- each model to predict the most accurate model
100 m MaleACTN3 R577X
minate 10.55 ±(rs1815739)
0.27 (n = 35) 10.58 ± 0.33 (nTaqMan®
alleles, = 44) 10.77 ± 0.31 (n = 10) 10.56 ± 0.32 (n = 47) 10.26 ± 0.35 (n = 22) 10.28 ± 0.30 (n = 11)
tested.
Pre-Designed
200 m Male SNP Genotyping Assay
21.19 ± 0.53 (n = 35) 21.29was
± 0.61used
(n = 36)(assay
21.86 ± 0.54* (n = 8) 21.17 ± 0.52 (n = 41) 20.53 ± 0.64 (n = 23) 20.98 ± 0.72 (n = 11)
ID: C_590093_1_), including appropriate primers and
400 m Male 46.90 ± 1.29 (n = 44) 47.41 ± 1.43 (n = 46) 47.55 ± 1.42 (n = 9) 46.82 ± 1.28 (n = 43) 46.49 ± 1.66 (n = 18) 47.29 ± 1.69 (n = 7)
fluorescently labeled (FAM and VIC) MGB™ probes to Results
*200-m (RRthe
detect vs. RX vs. XX) P < 0.016
alleles. The personal best 100-, 200- and 400-m sprint times
Genotyping of the ACE I/D polymorphism, in all co- (±SD), according to the ACTN3 and ACE genotype and
horts, was carried out as previously described [25]. distribution, are presented in Tables 1 and 2.
43.18-s in 400-m (current World record holder: Michael Statistical analysis
Johnson); in female sprinters of African ancestry, 10.49 s To compare the sprinters’ records between all geno-
Table
in 1002 The
m and100-m, 21.34200-m s inand200-m
400-m (current
best sprintWorld
times (average±SD)
record types in malesweaccording
used the to ACEone-way
I/D genotype distribution
analysis of variance
Caucasians African Ancestry
holder: Florence Griffith-Joyner); in the Caucasian male (ANOVA). The Tukey’s post-hoc test was used to de-
Running event/Genotype DD
sprinters, 9.99 s in 100-m (best recordIDholder: Christophe II
termineXX + II + ID
statistical DD ID
significant difference II
among the
100 m Male 10.62 ± 0.32 10.60 ± 0.29 10.70 ± 0.30 10.63 ± 0.29 10.07 + 0.38 10.27 + 0.32 10.35 + 0.49
Lemaitre), 19.72 s in 200-m (n = 33) (best record (n = 28)holder: (n Pietro
= 13) genotype
(n = 42)groups. The level of significance
(n = 5) (n = 13) was
(n = set
6) at
Mennea),
200 m Male and 43.45 s 21.33 in ±400-m
0.56 (best
21.25 ±record
0.51 holder: 0.05. 21.47
21.93 ± 0.67** Using the Simple
± 0.64** 20.53 +Interactive
0.70 20.47Statistical
+ 0.57 Analysis
21.16 + 0.42
Jeremy Wariner); and (nin= 27)female Caucasian (n = 24) sprinters,
(n = 11) website(n = (SISA;
36) www.quantitativeskills.com/sisa/)
(n = 9) (n = 11) geno-
(n = 4)
10.77-s
400 m Malein 100-m (best 46.94 record
± 1.19holder: 47.24Ivet Lalova)48.50
± 1.40 and type interactions
± 1.07** 47.49 ± 1.44** on46.57 sprint
+ 1.7 performance
47.08 + 1.29 were46.85
further
+ 1.52
(n = 35) (n = 43) (n = 11) (n = 58) (n = 11) (n = 7) (n = 4)
21.71 s and 47.60s in 200-m and 400-m respectively (best assessed using correlation analysis as previously de-
**200-m (DD vs. ID vs. II) P < 0.004; **400-m (DD vs. ID vs. II) P < 0.003
World(RRrecord
**200-m holder:
+ DD + RX see TableMarita
1 vs. XXKoch). scribed
+ II + ID) P < 0.002; **400-m (RR + DD + RX see [26].
Table 1 vs. XX + IIBriefly, three genetic models (additive
+ ID) P < 0.001
model and two dominant models assuming complete
dominance of each allele) were tested. The Additive
Genotyping genetic model consisted of 0, 0.5 and 1, to represent
Genomic DNA was isolated from buccal epithelium, or R allele homozygotes, RX heterozygotes and homozy-
white blood cells. The Australian, Greek, Italian, Lithu- gotes for the X allele, respectively; for the R allele
anian, US, Jamaican, Russian (from St Petersburg) and dominant or X allele dominant genetic models, the
Spanish sprinters’ DNA samples were genotyped using the corresponding values were 0, 0, 1 or 0, 1, 1, respect-
model. The percentage of observed variance (coefficient of was detected between the genotype combination of
determination, r2) explained by the ACE genotype using ACTN3 RR/RX and ACE DD with 200-m sprint speed
this recessive model was 1.48 % (Fig. 1b). (Tables 1 and 2). Given we have found a positive
Fig. 1 a Individual 200-m running times (±SD) in male Caucasian sprinters according to their ACTN3 R577X genotype and the qualifying times
(QT) for the Olympic Games (20.65 s). b Individual 200-m running times (±SD) in male Caucasian sprinters according to their ACE I/D genotype
Papadimitriou et al. BMC Genomics (2016) 17:285 Page 5 of 8
and the qualifying times (QT) for the Olympic Games (20.65 s)
(QT) for the Olympic Games (45.90s). b Individual 400-m running times (±SD) in male Caucasian sprinters according to their ACE I/D genotype
and the qualifying times (QT) for the Olympic Games (45.90s)
associations by independently examining the ACTN3 qualifying standard in 400-m (45.90s). Collectively, these
RR/RX and the ACE DD/ID genotypes in Caucasian findings suggest that the ACTN3 577XX and the ACE II
male 200-m sprint performance, we wondered whether genotypes are detrimental for 200- and 400-m sprint
the combination of these positive genotypes would have performance respectively.
cluded in this study, there were no cases of 577XX high performance level for the elite sprinters we studied.
sprinters who had faster best-personal running time than Thirdly, we have analysed quantitative measure with re-
2012 Olympic qualifying standard in 200-m (20.65 s), spect to ACTN3 and ACE genotypes to assess the genotype
and no cases of ACE DD sprinters who had best- effect size in both males and females separately. Only one
personal running time faster than 2012 Olympic previous study has taken a similar approach with 100-m
(QT) for the Olympic Games (10.24 s). b Individual 100-m individual running times (±SD) in male Caucasian sprinters according to their ACE I/D
genotype and the qualifying times (QT) for the Olympic Games (10.24-s)
MINI REVIEW
published: 18 December 2017
doi: 10.3389/fphys.2017.01080
ACTN3: More than Just a Gene for

Speed
Craig Pickering 1, 2* and John Kiely 1
Pickering and Kiely 1

School of Sport and Wellbeing, Institute of Coaching and Performance, UniversityACTN3: Adaptation,
of Central Lancashire, Preston, Recovery, and Injury
United Kingdom, 2 Exercise and Nutritional Genomics Research Centre, DNAFit Ltd., London, United Kingdom
Over the last couple of decades, research has focused on attempting to understand
TABLE 2 | Studies examining the interaction between ACTN3 genotype and the
exercise recovery.
genetic influence on sports performance. This has led to the identification of a
number of candidate genes which may help differentiate between elite and non-elite
Study Method Sample
athletes.characteristics
One of the most promising genes inMain outcome
that regard is ACTN3, which has commonly
been referred to as “a gene for speed”. Recent research has examined the influence
Pimenta et al., 2012 Eccentric-contraction based training 37ofmale professional
this gene on othersoccer players
performance Greater
phenotypes, creatine
including kinase
exercise (CK) activity
adaptation, in XX genotypes
exercise
session. based in Brazil. (n = 9 XX genotype). vs. RR.
recovery, and sporting injury risk. In this review, we identified 19 studies exploring
Clarkson et al., 2005b 50 maximal eccentric contractions of the 157 male
these (n = 78) and
phenotypes. female
Whilst No association
there was large variation of R577X
in the results withstudies,
of these increases
as in CK and
elbow flexor. subjects
well as of various heterogeneous
extremely ethnicities cohorts, myoglobin (Mb)a following
there is overall eccentric exercise.
tentative consensus that
(n ACTN3
= 115 Caucasians; = 48 the
genotype can nimpact XX phenotypes of interest. In particular, the R allele of a
genotype).
common polymorphism (R577X) is associated with enhanced improvements in strength,
Vincent et al., 2010 4 × 20 maximal single leg eccentric knee 19protection
healthy young
from males (n =
eccentric 10 XX
training-induced XX genotypes
muscle damage, hadandgreater
sportspeak CKThis
injury. activity
extensions. genotype).
illustrates that ACTN3 is more than just a gene post-training compared
for speed, with to RR
potentially genotypes, and
wide-ranging
influence on muscle function, knowledge of reported
which maygreater increases
aid in the in muscle pain.
future personalization
Venckunas et al., 2012 Two bouts of 50 drop jumps. 18ofyoung
exercise training
males (n =programmes.
9 XX genotype). RR showed greatest decrease in voluntary force, and
Edited by:
Kimberly Huey,
slower recovery, compared to XX genotypes.
Keywords: ACTN3, genetics, adaptation, recovery, injury, personalized, genetic testing
Djarova et al., 2011 Resting blood sample. Drake University, United States 31 South African Zulu males (n = 14 R allele associated with lower CK levels (RR vs. RX).
Reviewed by: Cricketers and n = 17 controls). No
Rudy Valentine, INTRODUCTION
Iowa State University, United States
XX genotypes.
Del Coso et al., 2017b Marathon race, pre- and post-race Moh H. Malek, 71ACTN3 is a gene that
experienced encodes
runners (n for
=8 alpha-actinin-3,
XX Xa allele
proteincarriers
expressedhad
onlyhigher
in type-II
CKmuscle
and fibers
Mb levels
Wayne State University, United States
Counter Movement Jump (CMJ). (North et al., 1999). A common polymorphism inpost-race
genotype). this gene is R577X (rs1815739),
compared to RRwhere a C-to-T
homozygotes. X allele
*Correspondence: base substitution results in the transformation of an arginine base (R) to a premature stop codon
carriers also had a greater reduction in leg muscle
Craig Pickering (X). X allele homozygotes are deficient in the alpha-actinin-3 protein, which is associated with a
craig@dnafit.com lower fast-twitch fiber percentage (Vincent et al., power
2007), butcompared to RR
does not result genotypes.
in disease (MacArthur
Del Coso et al., 2017a Triathlon competition (1.9 km swim, 75 km 23and North,experienced
healthy, 2004). The XX triathletes
genotype frequency differs
X allele across ethnichad
carriers groups,
a morewith approximately
pronounced jump height
(n 25% of males,
Asians, 18%
n =of5Caucasians, 11% of Ethiopians, 3% of Jamaican and USto African Americans, In X allele
Specialty section:
cycle, 21.1 km run), pre- and post-race
This article was submitted to
= 19 XX genotype). reduction compared RR genotypes.
and 1% of Kenyans and Nigerians possessing the XX genotype (Yang et al., 2007; MacArthur et al.,
CMJ. Exercise Physiology, carriers, there was a tendency toward higher
2008; Scott et al., 2010). ACTN3 genotype is associated with speed and power phenotypes. Yang et al.
a section of the journal post-race
(2003) reported that elite sprint athletes had significantly Mbfrequencies
higher concentrations
of the R(P = 0.10)
allele than and CK
Frontiers in Physiology
concentrations
controls, a finding that has been replicated multiple times in speed,(P = 0.06)
power compared
and strength athletesto RR
Received: 11 October 2017
(Druzhevskaya et al., 2008; Roth et al., 2008; Eynonhomozygotes.
et al., 2009; Ahmetov et al., 2011; Cieszczyk
Accepted: 08 December 2017
et al., 2011; Kikuchi et al., 2016; Papadimitriou et al., 2016; Weyerstraß et al., 2017; Yang et al.,
Belli et al., 2017 37.1 km adventure race (22.1 km 18 December 2017
Published: 20 well trained athletes (n = 15 XX genotypes had higher concentrations of serum
2017), although these findings are not unequivocal (Scott et al., 2010; Gineviciene et al., 2011; Sessa
mountain biking, 10.9 km trekking, 4.1 km Citation: males;
et al., n = 4Whilst
2011). XX genotype). Mb,toward
Yang et al. (2003) found a trend CK, lactate dehydrogenase
an increased (LDH) and AST
XX genotype frequency
Pickering C and Kiely J (2017) ACTN3:
water trekking, 30 m rope course). compared
in endurance athletes vs. controls, this relationship to Rwith
is less robust, allele
most carriers.
studies reporting a
More than Just a Gene for Speed.
Front. Physiol. 8:1080. lack of association between XX genotype and endurance performance (Lucia et al., 2006; Saunders
doi: 10.3389/fphys.2017.01080 et al., 2007; Döring et al., 2010; Kikuchi et al., 2016). In addition, whilst Kenyan and Ethiopian
TABLE 3 | Studies examining the interaction between ACTN3 genotype and sports injury.
post-race Mb concentrations (P = 0.10) and CK
concentrations (P = 0.06) compared to RR
homozygotes.
Belli et al., 2017 37.1 km adventure race (22.1 km 20 well trained athletes (n = 15 XX genotypes had higher concentrations of serum
mountain biking, 10.9 km trekking, 4.1 km males; n = 4 XX genotype). Mb, CK, lactate dehydrogenase (LDH) and AST
water trekking, 30 m rope course). compared to R allele carriers.
TABLE 3 | Studies examining the interaction between ACTN3 genotype and sports injury.
Study Method Sample characteristics Main outcome
Iwao-Koizumi et al., Sports injury data survey. 99 female students (n = 34 XX genotype). R allele associated with an increased odds ratio
2015 (OR) of 2.52 of muscle injury compared to X allele.
Deuster et al., 2013 Controls–lower body exercise test. 134 controls and 47 ER patients (n = 38 XX XX genotypes 2.97 times more likely to be to ER
Cases–anonymous blood or tissue genotype) cases compared to R allele carriers.
sample collected after an exertional
rhabdomyolysis (ER) incident.
Qi et al., 2016 Ankle sprain case-control analysis. 100 patients with non-acute ankle sprain vs. Significantly lower frequency of RR genotype in
100 healthy controls (n = 89 XX genotype). ankle sprain group compared to controls
(p = 0.001).
Kim et al., 2014 Ankle injury case-control analysis. 97 elite ballerinas and 203 normal female XX genotypes 4.7 times more likely to suffer an
adults (n = 65 XX genotype). ankle injury than R allele carriers.
Shang et al., 2015 Ankle injury case-control analysis. 142 non-acute ankle sprain patients and 280 RR genotype and R allele significantly
physically active controls (n = 87 XX genotype). under-represented in the acute ankle injury group.
All military recruits.
Massidda et al., 2017 Case control, genotype-phenotype 257 male professional Italian soccer players XX players were 2.6 times more likely to suffer a
association study. and 265 non-athletic controls. sports injury than RR genotypes. Severe injuries
were also more likely in X allele carriers compared to
RR genotypes.
recruits reporting ankle sprains. Finally, Massidda et al. (2017) Regarding ER, the likely mechanism is similar to that
decreased flexibility in the same test. This lack of consensus is The results of this mini-review indicate that, aside from its
largely due to the small total study number, with greater clarity established role in sporting performance, the ACTN3 R577X
FIGURE 1 | A summary of the potential wider implications of ACTN3 genotype on outcomes from exercise.
Frontiers in Physiology | www.frontiersin.org 5 December 2017 | Volume 8 | Article 1080

9q34
c
g-induced HR adaptation BASIC SCIENCES tion in submaximal exercise HR (Fig. 2), and found that in-
ximal heritability estimate
Special Report dividuals carrying less than 10 of these alleles did not reduce
their submaximal exercise HR with training, whereas those
had performed a linkage Advances with more inthan Exercise,
15 favorable alleles
j1
Fitness, elicited an and average HR
markers spread across the reduction of È20 beatsImin as a result of exercise training.
Performance
ocus as being significantly
Genomics in 2012
Overall, this study identified novel genetic variations as-
l exercise HR in response sociated with the response of submaximal exercise HR to
LOUIS PÉRUSSE1, TUOMO RANKINEN2, JAMES M. HAGBERG3, RUTH J. F. LOOS4, STEPHEN M. ROTH3,
d this up with a moreMARK in- A. SARZYNSKI2, BERND WOLFARTH5, and CLAUDE BOUCHARD2
nd found that a common 1
Department of Kinesiology, Laval University, Ste-Foy, Québec, CANADA; 2Human Genomics Laboratory, Pennington
Biomedical Research Center, Baton Rouge, LA; 3Department of Kinesiology, School of Public Health, University of Maryland,
element binding protein College Park, MD; 4The Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute of
% of the variance in Personalized
the Medicine, Mindich Child Health and Development Institute, The Ichan School of Medicine at Mount Sinai,
New York, NY; and 5Preventive and Rehabilitative Sports Medicine, Technical University Munich, Munich, GERMANY
o training (25). However,
ated that heritability, that ABSTRACT
4% of the interindividual PÉRUSSE, L., T. RANKINEN, J. M. HAGBERG, R. J. F. LOOS, S. M. ROTH, M. A. SARZYNSKI, B. WOLFARTH, and
C. BOUCHARD. Advances in Exercise, Fitness, and Performance Genomics in 2012. Med. Sci. Sports Exerc., Vol. 45, No. 5,
eft È30% of the variation mouse pp. 824–831, 2013. A small number of excellent articles on exercise genomics issues were published in 2012. A new PYGM knock-in
model will provide opportunities to investigate the exercise intolerance and very low activity level of people with McArdle disease.
d for, even after consid- New reports on variants in ACTN3 and ACE have increased the level of uncertainty regarding their true role in skeletal muscle metabolism
and strength traits. The evidence continues to accumulate on the positive effects of regular physical activity on body mass index or adiposity
urther refine the genetic in individuals at risk of obesity as assessed by their FTO genotype or by the number of risk alleles they carry at multiple obesity-susceptibility
2 study, they performed loci. The serum levels of triglycerides and the risk of hypertriglyceridemia were shown to be influenced by the interactions between a single
nucleotide polymorphism (SNP) in the NOS3 gene and physical activity level. Allelic variation at nine SNPs was shown to account for
o identify additional loci the heritable component of the changes in submaximal exercise heart rate induced by the HERITAGE Family Study exercise program.
SNPs at the RBPMS, YWHAQ, and CREB1 loci were found to be particularly strong predictors of the changes in submaximal exercise
xercise HR response to heart rate. The 2012 review ends with comments on the importance of relying more on experimental data, the urgency of identifying
results across the 22 au- panels of genomic predictors of the response to regular exercise and particularly of adverse responses, and the exciting opportunities
offered by recent advances in our understanding of the global architecture of the human genome as reported by the Encyclopedia of DNA
They found 40 individ- Elements project. Key Words: GENETICS, EXERCISE TRAINING, PHYSICAL ACTIVITY, CANDIDATE GENES, GENE–EXERCISE
INTERACTION, SINGLE NUCLEOTIDE POLYMORPHISM, QUANTITATIVE TRAIT LOCUS, GENOMIC PREDICTORS
the HR response (all P G
T
osely associated with the his installment FIGURE of the2—Exercise training-induced
2012 exercise genomics review changes
review in ‘‘scientifically
of the HR at 50 Wstrongest (adjustedand substantively most
summarizes age, sex, BMI, and initial HR response) across eight GWAS SNPAs described in the
the most significant articles published in important articles in exercise genomics.’’
se HR changes were both the pastfor calendar year in the area of genomics of ex- introduction to the first such review (26), a secondary aim
summary score categories in white subjects from the HERITAGE Family
osine 3-monooxygenase/ ercise, fitness, and performance. The review is not intended to
Study. The number of participants
of this effort is to help exercise scientists identify the gaps in
be a comprehensive and cumulative summary of all published within our each
knowledgecategory is indicated
concerning genomics in-and genetics relative
ation protein, theta poly- side or below each box. Reproduced
literature of the past year in exercise genomics. Rather, the from Rankinen et al. (27).
to exercise, fitness, and performance and thereby to provide
article focuses only on the strongest studies as evaluated by direction for future investigative efforts and improved
design, sample size, phenotypes, novelty, and potential im- study designs.
pact. The present article is the fourth annual version of the Med. Sci. Sports Exerc., Vol. 45, No. 5, pp. 824–831, 2013
In this review, we have selected articles focusing on (a)
physical activity behavior and exercise intolerance, (b) mus-
College of Sports Medicine cularhttp://www.acsm-msse.org
strength and power, (c) cardiorespiratory fitness and
Address for correspondence: Claude Bouchard, Ph.D., Human Genomics endurance performance, (d) body weight and adiposity, (e)
strength of the associations. The individual variants and netic predisposition for elevated seru
BASIC SCIENCES
SNP scores now need to be tested in independent studies to
examine whether these associations can be replicated and to
HEMODYNAMIC TRAITS
potentially identify other predictors of TG response to ex-
Advances in Exercise, Fitness, and
ercise. Furthermore, replication studies are needed to ex-
amine whether these results apply to other modes and doses
Few genetic association studies w
the relationship between acute or c
Performance Genomics in 2015
of endurance exercise. modynamic traits or cardiovascular o
In the second study, Justesen et al. (20) examined whether small sample sizes (N G 100). Despi
MARK A. SARZYNSKIlifestyle1, factors
RUTH J. F.modified
LOOS2, ALEJANDRO the association LUCIA3, LOUIS of lipid-based
PÉRUSSE4, STEPHEN powered
M. ROTH studies,
5
, some are worth m
6 7 7
BERND WOLFARTH , TUOMO RANKINEN , and CLAUDE
genetic risk scores (GRS) with serum lipid traits in two BOUCHARD can help understand the genetic basi
1
Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, SC; 2The
vascular Genetics and ii) human var
outcomes
of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine, The Mindich
Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY; these 3 outcomes
Universidad Europea to exercise intervent
4
and Research Institute, Hospital 12 de Octubre (i+12), Madrid, SPAIN; Faculty of Medicine, DepartmentAof recent Kinesiology, meta-analysis of cand
Laval University, Ste-Foy, Québec, CANADA; 5Department of Kinesiology, School of Public Health, University of Maryland,
College Park, MD; 6Department of Sport Medicine, Humboldt University and Charité University School studies of the
of Medicine, blood pressure respon
Berlin,
7
GERMANY; and Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, exercise
LA included data from 12 ae
studies examining up to 11 candida
ABSTRACT (9). Participants (total N = 3444;
SARZYNSKI M. A., R. J. F. LOOS, A. LUCIA, L. PÉRUSSE, S. M. ROTH, B. WOLFARTH, T. RANKINEN, and C. Hispanic
BOUCHARD.middle-age adults (44 T
Advances in Exercise, Fitness, and Performance Genomics in 2015. Med. Sci. Sports Exerc., Vol. 48, No. 10, pp. 1906–1916, 2016. This
with prehypertension (systolic blo
review of the exercise genomics literature encompasses the highest-quality articles published in 2015 across seven broad topics: physical
11.8insulin
activity behavior, muscular strength and power, cardiorespiratory fitness and endurance performance, body weight and adiposity, mm and Hg; diastolic blood pre
glucose metabolism, lipid and lipoprotein metabolism, and hemodynamic traits. One study used a quantitative trait locus for wheel running
9.6 mm Hg) after a ‘‘standard’’ mo
in mice to identify single nucleotide polymorphisms (SNPs) in humans associated with physical activity levels. Two studies examined the
association of candidate gene ACTN3 R577X genotype on muscular performance. Several studies examined gene–physical V̇O2peak
activity )in-aerobic training program (t
week of ~40 min per session, for an
teractions on cardiometabolic traits. One study showed that physical inactivity exacerbated the body mass index (BMI)–increasing effect of
an FTO SNP but only in individuals of European ancestry, whereas another showed that high-density lipoprotein cholesterol (HDL-C) SNPs
Of the polymorphisms examined (A
from genome-wide association studies exerted a smaller effect in active individuals. Increased levels of moderate-to-vigorous–intensity
CHRM2Oners324640 and rs819199
physical activity were associated with higher Matsuda insulin sensitivity index in PPARG Ala12 carriers but not Pro12 homozygotes.
study combined genome-wide and transcriptome-wide profiling to identify genes and SNPs associated with the response of triglycerides (TG)
to exercise training. The genome-wide association study results showed that four SNPs accounted for all of the heritability rs1049255,
of ¸TG, GNB3 rs5443, IL6R r
whereas the baseline expression of 11 genes predicted 27% of ¸TG. A composite SNP score based on the top eight SNPsand derivedTGFA1
from the rs1800470), only the
genomic FIGURE 3—Adjusted
and transcriptomic analyses wasmean response
the strongest toofexercise
predictor training
$TG, explaining 14% oftriglycerides
the variance. The review concludes with a
($TG)
discussion acrossframework
of a conceptual eight SNPdefiningsummary score
some of the critical categories
conditions in genomics
for exercise HERITAGE Met235Thr
studies and highlights the importance (rs699) variant was ass
Caucasian
of the recently subjects.
launched Valuesof were
National Institutes adjusted
Health Common forprogram
Fund age, titled
sex,‘‘Molecular
baselineTransducers
BMI, of Physical in DBP Activity(post-
in vs pretraining, P = 0
andKey
Humans.’’ baseline TG level.SINGLE
Words: GENETICS, The number
NUCLEOTIDE of participants
POLYMORPHISM, within each SNP ASSOCIATION STUDY,
GENOME-WIDE
GENETIC score
RISKcategory is indicated inside
SCORE, GENE-EXERCISE each histogram
INTERACTION, bar. From Sarzynski
DIRECT-TO-CONSUMER GENETIC TESTS G1% of the variance in the DBP r
et al. (34) with permission. Reductions in DBP were greater amo
T
his publication is the latest installment of an annual
publications as defined by study design, sample size, analyt-
publication on exercise genetics and genomics. It
ical strategy, novelty, and relevance of phenotypes with po-
Med. Sci. Sports Exerc., Vol. 48, No. 10, pp. 1906–1916, 2016.
summarizes the scientific literature reported in the cal-
tential implications for exercise science and sports medicine.
endar year 2015. The review focuses on the strongest
The review is not a comprehensive summary of all published
ADVANCES IN EXERCISE GENOMICS 2015 Medicine & Science in S
articles on genetics and genomics relative to exercise, physi-
cal activity, fitness, and performance, and standards for the
Address for correspondence: Claude Bouchard, Ph.D., Human Genomics
final performance is quantifiable can be considered latter discussed in this review.
Asociación entre
contribución genética
y tipos de deportes
FIGURE 1 - Contribution of genetic factors to performance-relevant quantitative traits.

Vo2 máx
Qué tan heredable es?
two other estimates (123 and 138 ml O2 , respectively) we explored whether the fluctuations in achieved heart
obtained by Shephard et al. (2004) on the same dataset rates and workloads compared to targeted levels for each
but with less input data for the computation of the SD exercise session were contributing to the variability in
of repeated tests. How can this remaining variability in training responses. We observed that the fluctuations in
V̇O2 max trainability be accounted for and can the dissection workloads accounted for about 6% of the V̇O2 max training
50 47
Percent variance explained 40
30
20
20
10
6
2 3 3 3 3
0
e e x ht ity ed ro
r
ilit
y
e lin x Ag Se ei
g ic e t
e r b
s ma hn rg l s a
a
B O2
W Et ta W i ca y ∆ erit
V vs ∆ n il
ch da
H
e d n g e
v i T &
h ie rain
t
Ac
483 white subjects, 259 black subjects, 17–65 years of age; Mean gain = 384 mL O2, SD = 202
Figure 1. A summary of the correlates of the gains in V̇ O2 max in the HERITAGE Family Study
The contributions of various correlates in terms of percentage variance accounted for in V̇O2 max response are
shown. Details are provided in the text.
C 2016 The Authors. The Journal of Physiology ⃝

⃝ C 2016 The Physiological Society
J Physiol 595.9 (2017) pp 2931–2939
SYMPOSIUM REVIEW
were included. First, a regression model with132,127,094
backward elimination
Downloaded from on September 27, 2014

rs10452621 6 ENPP3 (17 kb) 0.12 0.005 0.486 4.04 0.0451
ymphoblastoid was used to filter out redundant
J Appl Physiol 110:SNPs [mainly
1160–1170, due to a strong pairwise
2011.
ntra Systems, V̇O2max
linkage disequilibrium
First training
(LD)].
published responses23,were
The threshold
December 2010;adjusted
for for age,
keeping thesex,
SNPsand in
baseline V̇O2max (see METHODS). Gene indicates the gene located nearest to the SNP. The distance
doi:10.1152/japplphysiol.00973.2010.

sing Illumina to the gene in kb (1,000 bp) is shown
the model was P % 0.05. SNPs that were retained in the final in parentheses. If no distance is shown, the SNP is located within the gene locus.
a BeadStation backward elimination model were then analyzed with a multivariate
Illumina Ge- regression model using forward selection.
he same batch Associations Genomic predictors of the maximal O uptake response to standardized
considerable
between theindividual differences
V̇O2max training responsein the
andmagnitude
replica- of bene-
2 Why do we have such human variation in human adaptive
udio genotype tion SNPs werefits derived from a physically active lifestyle (4, 20, 26, 45). capacity? From a prior report (8), we know that the heritability
analyzed using the MERLIN association model in
and confirmed HERITAGE Thus, exercise training programs
blacks the andheterogeneity
with general linearin themodels
response (Proc GLM
in V̇ O2max inranges from of the response variance adjusted for age, sex, and baseline
e heterozygote SAS version 9.1) in DREW and STRRIDE subjects. Data adjustment
ered out with zero or very low gains up to !50%. In a series of intervention V̇O2max is in the range of 45–50%. The present study showed
in HERITAGE blacks was done the same way 1 as in HERITAGE 1
confirmed all studiesand
whites. For DREW performed
Claudewith
STRRIDE, age,identical
Bouchard, twins,A.
Mark
sex (STRRIDE weSarzynski,
only), (4,base-
36) found Trevathat that2 almost
K. Rice, William50% of the
E. Kraus, 3
varianceS.inChurch,
Timothy 4
age, sex, and baseline
mple mix-ups. the between-identical
Yun Ju twin
Sung, pairs
2
D. variance
C. Rao,
line V̇O2max, and intervention group were used as covariates in the
2
in
and response
Tuomo to regular
Rankinen 1
level-adjusted V̇ O 2max response to an exercise program can be
Minor allele GLM model. exercise was 1from
In these replication two to
samples, nine
we times
retained larger
SNPs than the
signifi- within-pair predicted with a panel of 21 SNPs
2
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana; Division of Biostatistics, in 473 whites from the
Weinberg equi- cant at the 0.05 level. for cardiorespiratory
variance fitness, hemodynamic, and met- HERITAGE
3 Family Study, indicating
Washington University School of Medicine, St. Louis, Missouri; Department of Cardiovascular Medicine, Duke University a high degree of con-
r 55 (0.017%) abolic phenotypes.
es were geno- School ofThese
Medicine, observations
Durham, North were amplified
Carolina; and cordance
and 4Laboratory between
of Preventive the Research,
Medicine heritability level and
Pennington the variance ac-
Biomedical
RESULTS confirmed byResearch the HERITAGE Family
l the SNPs. Center, Baton Rouge,Study (8, 10, 37).
Louisiana counted for by the panel of 21 SNPs. Interestingly, each of six
The distribution of V̇O 2max changes
of these SNPs accounted for at least 3% of the variance in the
nal regression Submitted 20 Augustwith
2010; the HERITAGE
accepted in final form 17 December 2010
of these SNPs exercise training program is shown in Fig. 1 for the whites. V̇O2max response. This observation is in sharp contrast with the
design scores About 7% ofTable subjects3. Distribution
registered a of theofV̇O100
gain response
2maxml/min (in ml/min)
or less, numerous reports on the effect size of SNPs associated with
Bouchard C, Sarzynski MA, Rice TK, Kraus WE, Church TS, sitting for prolonged periods, are all associated with less
1.1; values of whereas 8%GWAS ofSung predictor
subjects improvedSNP by summary
700 scores
ml/min orinmore.
HERITAGEOn whites
YJ, Rao DC, Rankinen T. Genomic predictors of the maximal favorable cardiovascular and diabetes risk profiles, increased
cessful assay),
tabase to find O2 uptake response
Score to standardizedFrequency
No. of Subjects exercise training Mean programs. J Appl SE morbidities, and higher mortality from all causes and from
h rs17117533 Physiol 110: 1160 –1170, 2011. First published December 23, 2010; cardiovascular diseases (3, 6, 18, 30, 35, 40, 42). To alleviate
7 4
doi:10.1152/japplphysiol.00973.2010.—Low 0.8 258.8
cardiorespiratory 24.1
fitness
10921078 was 8 a powerful predictor
13 of morbidity and 2.62 38.5 the health burden associated with sedentary behavior and poor
score % 0.96). is cardiovascular188.7mortality. In 473
9 19 3.82 204.7 34.0 fitness, public health recommendations are that adults be phys-
immortalized sedentary adults, all whites, from 99 families of the Health, Risk Factors,
Exercise Training, and Genetics (HERITAGE) Family Study, the heri- ically active at moderate intensity most days of the week (6, 35,
10 25 5.43 204.5 34.7
(DREW and 11 28 6.44 269.4 31.2 42). The assumption is that as people become more active, they
). SNPs were tability of gains in
12 54 maximal O2 uptake 11.27(V̇O2max) after 302.2exposure to 22.9
a

standardized 20-wk exercise program was estimated at 47%. A genome- increase cardiorespiratory fitness, thereby reducing the risk of
Veracode tech- 13 57 12.07 349.5 20.6
ere done using wide
14 association study
48 based on 324,611
10.46 single-nucleotide
386.2 polymor- 22.3 disease and premature death. This approach has been validated
e call rate was phisms (SNPs) was
15 60 undertaken to identify
12.88 SNPs associated 393.9 with im- 24.8 in several studies (2, 21). Cardiorespiratory fitness levels are
TAGE: 100%, provements
16 in V̇O51
2max Based on single-SNP
11.47 analysis, 39
480.8 SNPs were26.8 also more strongly related to health outcomes than are general
SNPs showed associated with the
17 28 gains with P ! 6.04 1.5 " 10#4. Stepwise
594.5 multiple35.2 physical activity levels (17, 23).
s were in HWE regression analysis27of the 39 SNPs identified
18 5.84 a panel515.3
of 21 SNPs that 31.6 Maximal O2 uptake (V̇O2max), the maximal amount of O2 per
e PEDSTATS accounted for 49%25of the variance in V̇
19 O2max trainability.
5.23 503.1Subjects who 30.6 unit of time that can be delivered to peripheral organs, includ-
e du Polymor- carried !9 favorable
20 12 alleles at these 212.41 SNPs improved505.5 their V̇O2max by 31.0 ing skeletal muscle, where it is used to sustain muscular
36 53 54 57 48 60 51 55 52
O
HapMap Phase 21
221 ml/min, whereas 6 those who carried 1.21
"19 of these 827.6alleles gained, 117.0
on
contraction at peak exercise, is considered the gold standard
.
22 1 0.2
average, 604 ml/min. The strongest association was with rs6552828, 557
A10860, and
23
located in the acyl-CoA1 0.2
synthase long-chain member 747 1 (ACSL1) gene, measure of cardiorespiratory fitness. V̇O2max is characterized
e between the 24 .
which 2 0.4 727.5
accounted by itself for $6% of the training response of V̇O2max . by wide interindividual differences even among sedentary
189.5
the HapMap O Fig. 3.For
Age, sex, and in
baseline V̇O2max-adjusted V̇O2max training
Exerciseresponses
n GoldenGate The genes nearest to the SNPs that were the strongest predictors were PR adults.
28 2 0.4 800.4 56.6
across nine
instance,
GWAS
the Health,
predictor
Risk Factors,
single-nucleotide polymorphism (SNP) score
Fig. 1. Distribution
29 of the maximal O uptake (V̇ ) training responses in
confirmed by domain-containing 11 with ZNF domain
2 O2max 0.2(PRDM1); glutamate
894.7 receptor, Training, and Genetics (HERITAGE) Family Study, the heri-
categories in HERITAGE whites. Numbers of subjects within each SNP score
whites in the Health,
31 Risk Factors, Exercise
2 Training, and Genetics
0.4 (HERITAGE)
1062 35.5
Family Study. ionotropic, N-methyl-D-aspartate 3A (GRIN3A); K channel, voltage tability
% of V̇
category areO2max in the
indicated untrained
inside state adjusted
each histogram bar. Le, for
“lessage, sex, to;” ge,
or equal
gated, subfamily H, member 8 (KCNH8); and zinc finger
The summary score was calculated using the 21 SNPs shown in Table 2. protein of the body mass, and body
“greater or equal to.” composition was estimated at $50% (7),
cerebellum 4 (ZIC4). The association with the SNP nearest to ZIC4 was a level comparable with what has been observed in other
Physiol • VOL 110 • MAY 2011 • www.jap.org
replicated in 40- to 65-yr-old, sedentary, overweight, and dyslipidemic family studies and in sets of identical and fraternal twins (11).
subjects trained in Studies of a Targeted Risk Reduction J Appl Physiol • VOL 110 • MAY 2011 • www.jap.org
Intervention However, little is known about the genes and DNA sequence
Through Defined Exercise (STRRIDE; n & 183). Two SNPs were variants that account for this genetic effect (12). Regular
replicated in sedentary obese white women exercise trained in the Dose
exercise is the most effective way to augment cardiorespiratory
Response to Exercise (DREW) study (n & 112): rs1956197 near dishev-
elled associated activator of morphogenesis 1 (DAAM1) and rs17117533
fitness, as evidenced by an increase in V̇O2max J ApplorPhysiol
an improved
110: 1160–1170, 2011
in the vicinity of necdin (NDN). The association of SNPs rs884736 in the tolerance to a given absolute level of submaximal exercise.
calmodulin-binding transcription activator 1 (CAMTA1) locus and There are considerable individual differences in V̇O2max
rs17581162 $68 kb upstream from regulator of G protein signaling 18 responses to exercise training. In the HERITAGE Family
(RGS18) with the gains in V̇O2max in HERITAGE whites were replicated Study, 473 adult whites from 99 nuclear families completed a
Cantidad de fibras lentas
• The peroxisome proliferator-activated receptor α
gene (PPARA) intron 7 G/C polymorphism
(rs4253778) is associated with muscle fibre type
composition in young men, i.e. GG homozygotes
had significantly higher percentages of type I fibres
(55.5 ± 2.0 vs. 38.5 ± 2.3%, P = 0.003) than CC
homozygotes (Ahmetov et al. 2006)
Eur J Appl Physiol (2006) 97: 103–108
DOI 10.1007/s00421-006-0154-4
ORIGINAL ARTICLE
Ildus I Ahmetov Æ Irina A Mozhayskaya

David M Flavell Æ Irina V Astratenkova
Antonina I Komkova Æ Ekaterina V Lyubaeva
Pavel P Tarakin Æ Boris S Shenkman
Anastasia B Vdovina Æ Aleksei I Netreba
Daniil V Popov Æ Olga L Vinogradova
Hugh E Montgomery Æ Viktor A Rogozkin
PPARa gene variation and physical performance in Russian athletes

106
Accepted: 23 January 2006 / Published online: 28 February 2006
Table 2 PPARa 2006
! Springer-Verlag intron 7 genotype distribution and frequencies of PPARa gene C allele in athletes stratified by power/endurance
orientation and sporting discipline. Comparison with controls was by v2 test
Abstract Peroxisome proliferator-activated receptor a with increasing anaerobic component of physical per-
(PPARa)
Group regulates genes
Sport responsible for skeletal
n and formance (P=0.029). PGG
Genotype value genotype frequencies
C allele, % P value in
heart muscle fatty acid oxidation. Previous studies have endurance-oriented and power-oriented athletes were
shown that the PPARa intron 7 G/C polymorphism was GG, %80.3 GC,and % 50.6%,
CC, %respectively, and were significantly
associated with left ventricular growth in response to (P<0.0001) different compared to controls (70.0%). To
exercise. We speculated that GG homozygotes should be examine the association between PPARa gene variant
Endurance-oriented
more prevalent withinSwimming 24
a group of endurance-oriented 91.7 and fiber
8.3 type 0 composition,
0.068 muscle 4.2 biopsies 0.023*
from m.
events have normal (800–1,500
athletes, fatty acidm) metabolism, and in- vastus lateralis were obtained and analyzed in 40 young
creased percentages of Cross-country
slow-twitch skiing
fibers. We have 88.7 men. 9.7GG homozygotes
62 tested 1.6 0.006*(n=25) 6.4 had significantly
0.003*
this hypothesis in the Triathlon
study of a mixed cohort 30 of 786
86.7 (P=0.003)
13.3 higher
0 percentages
0.129 of
6.7 slow-twitch
0.043*fibers
Russian athletes in 13 different sporting disciplines (55.5±2.0 vs 38.5±2.3%) than CC homozygotes (n=4).
Biathlon
prospectively stratified by performance (endurance-
28 85.7 14.3 0 0.178 7.1
In conclusion, PPARa intron 7 G/C polymorphism was
0.063
Skating (3,000–5,000
oriented athletes, power-oriented m) and33athletes
athletes 87.9 associated
9.1 with3.0physical
0.657 7.6
performance 0.055 ath-
in Russian
Road cycling
with mixed endurance/power activity). PPARa 63intron79.4
7 letes,17.5 3.1 be explained,
and this may 0.228 11.9
in part, by the0.183
associ-
Rowing
genotype and allele frequencies were compared 251 74.9 ation23.1
to 1,242 between 2.0
PPARa 0.281
genotype 13.5 0.113 type
and muscle fiber
controls. We found anAllincreasing linear trend of 80.3 composition.
491C allele 17.9 1.8 0.0001* 10.8 0.0001*
Events with mixed Boxing 22 72.7 22.7 4.6 0.817 15.9 0.933
Keywords PPARa Æ Polymorphism Æ Fatty acids Æ
IldusPower/endurance
I Ahmetov (&) Æ I. A IceMozhayskaya
hockey 15 73.4 13.3 13.3 0.032* 20.0
Muscle fiber type Æ Physical performance
0.595
Irina(acyclic) activity Æ Antonina
V Astratenkova Wrestling
I Komkova 63 63.5 30.2 6.3 0.199 21.4 0.138
V. A Rogozkin
Court tennis 15
Sports Genetics Laboratory, St Petersburg Research Institute
66.7 20.0 13.3 0.047* 23.3 0.308
All Street, 197110,
of Physical Culture, 2 Dynamo 115 67.0 25.2
Introduction 7.8 0.012* 20.4 0.115
St Petersburg, Russia
Power-oriented Running (60–400 m) 77 55.8 41.6 2.6 0.025* 23.4 0.024*
E-mail: genoterra@mail.ru Peroxisome proliferator-activated receptor a (PPARa) is
Tel.:events
+7-812-2371936 Weightlifting 30 53.3 40.0 6.7 0.107 26.7 0.034*
a transcription factor that regulates lipid, glucose, and
Fax: +7-812-2370461 Skating (500 m) 39 43.6 53.8 2.6 0.001* 29.5
energy homeostasis and controls body weight and vas-
0.002*
D. M Flavell Swimming (50–100 m) 34 44.1 cular44.1 11.8
inflammation. 0.0004*
PPARa 33.8
is expressed 0.0002*
at high levels in
Centre for Cardiovascular All 180
Genetics, Department of Medicine, 50.6 44.4that catabolize
tissues 5.0 0.0001*
fatty acids,27.2 0.0001*
notably liver, skeletal
Royal Free and University College London Medical School,
Totals
The Rayne Institute, 5 University Street, 786 71.5 25.1 and heart,
muscle, 3.4 and 0.397
at lower 16.0 0.725
levels in other tissues,
Controls
WC1E 6JF, London, UK 1242 70.0 27.3 pancreas
including 2.7 (Braissant
1.000 16.4 1996). The
et al. 1.000
level of
expression of PPARa is higher in type I (slow-twitch)
Ekaterina V Lyubaeva Æ P. P Tarakin Æ B. S Shenkman than in type II (fast-twitch) muscle fibers (Russel et al.
A. *P<0.05
B Vdovinastatistically
Æ Aleksei significant
I Netreba differences
Æ Daniil V Popov
O. L Vinogradova
2003).
SSC RF Institute for Biomedical Problems, 76A Khoroshevskoe Endurance training increases the use of non-plasma
Chaussee, 123007, Moscow, Russia fatty acids and may enhance skeletal muscle oxidative
It is worth mentioning that intron 7 C allele frequency
H. E Montgomery
was found by
capacity bothPPARa
in men regulation
[n=131, frequency
of gene 26.7% vs.
expression
(Russel et al. 2003; Horowitz et al. 2000). PPARa reg-
significantly correlated with elite athlete status. Linear
Institute for Human Health and Performance, University College
London, N19 5LW, London, UK
controls (frequency 17.1%); P=0.0006] and women
ulates the expression of genes encoding several key
trends for increasing allele frequencies were also ob- [n=49, frequency 28.6% vs. controls (frequency
significantly correlated with elite athlete status. Linear controls (frequency 17.1%); P=0.0006] and women
trends for increasing allele frequencies were also ob- [n=49, frequency 28.6% vs. controls (frequency
served with by ‘elite’ status for both power-oriented 15.6%) P=0.003].
Eur J Appl Physiol (2006) 97: 103–108
(29.6% of DOIC10.1007/s00421-006-0154-4
allele frequency in elite athletes (n=27), Interestingly, muscle fiber typing of 40 men showed
P=0.0316)Oand endurance-oriented disciplines (92.2% of
RIGINAL ARTICLE
significant correlation between PPARa intron 7 poly-
G allele frequency in elite athletes (n=34), P<0.0001). morphism and muscle fiber specification. Mean per-
We also investigated the association of PPARa in- centages of type I fiber in GG homozygotes (n=25),
tron 7 polymorphism
Ildus I Ahmetovwith physical
Æ Irina performance sepa-
A Mozhayskaya
David M Flavell Æ Irina V Astratenkova
heterozygotes (n=11) and CC homozygotes (n=4) were
rately in Antonina
male and female Æ athletes
I Komkova Ekaterina (Fig. 2). Amongst
V Lyubaeva 55.5±2.0, 44.7±2.6 and 38.5±2.3%, respectively
Pavel P Tarakin Æ Boris S Shenkman
endurance-oriented
Anastasia B athletes, C alleleI Netreba
Vdovina Æ Aleksei frequency in both (r=0.55, P=0.0002). Furthermore, mean percentages of
men (n=335,
Daniil V Popov Æ
frequency 11.6%, P=0.004) and women
Olga L Vinogradova type II fibers in GG homozygotes, heterozygotes and CC
Hugh E Montgomery Æ Viktor A Rogozkin
(n=156, frequency 9.0%, P=0.007), was significantly homozygotes were 48.4±2.2, 58.1±3.3 and 61.0±2.1%,
PPARa gene variation and physical performance in Russian athletes
different compared to controls. Similarly, in power- respectively (r=!0.48, P=0.0015). Mean CSA of type I
oriented events group the strong association of C allele fiber in GG homozygotes was slightly bigger compared
Accepted: 23 January 2006 / Published online: 28 February 2006 to heterozygotes and CC homozygotes (5,479±274 vs
! Springer-Verlag 2006
30 5,122±520
35 and 4,952±493 lm2, respectively), but thispotential influ
Abstract Peroxisome proliferator-activated receptor a with increasing anaerobic component of physical per-
(PPARa) regulates genes responsible for skeletal and correlation was non-significant.
formance (P=0.029). Males
GG genotype frequencies in ber differenti
25 30
C allele frequency, %
heart muscle fatty acid oxidation. Previous studies have endurance-oriented and power-oriented athletes were
shown that the PPARa intron 7 G/C polymorphism was Females
80.3 and 50.6%, respectively, and were significantly
have relativel
in the trained
C allele frequency
associated with left ventricular growth in response to (P<0.0001)
25 different compared to controls (70.0%). To
20 exercise. We speculated that GG homozygotes should be examine the association between PPARa gene variant
more prevalent within a group of endurance-oriented and fiber type composition, muscle biopsies from m. fast-twitch fib
15 athletes, have normal fatty acid metabolism, and in- Discussion 20
vastus lateralis were obtained and analyzed in 40 young performance
creased percentages of slow-twitch fibers. We have tested men. GG homozygotes (n=25) had significantly
this hypothesis in the study of a mixed cohort of 786 15
(P=0.003) higher percentages of slow-twitch fibers though geno
10 Russian athletes in 13 different sporting disciplines
This is the first study to demonstrate that variationproportion.
(55.5±2.0 vs 38.5±2.3%) than CC homozygotes (n=4).
in
prospectively stratified by performance (endurance- In conclusion, PPARa intron 7 G/C polymorphism was
5
oriented athletes, power-oriented athletes and athletes the PPARa is associated with physical performance inOur study
10
associated with physical performance in Russian ath-
with mixed endurance/power activity). PPARa intron 7 letes, and this may be explained, in part, by the associ- functional dat
genotype and allele frequencies were compared to 1,242 athletes and correlated with their elite status. Specifi-
5 between PPARa genotype and muscle fiber type
ation
0 controls. We found an increasing linear trend of C allele composition.
cally, the intron 7 C allele seems associated with power- addressed wi
Controls Aerobic group Mixed group Anaerobic group 0 association o
Ildus I Ahmetov (&) Æ I. A Mozhayskaya
orientated
Keywords disciplines, andperformance
PPARa Æ Polymorphism
Æ
the G-allele with Æ endurance
Æ Fatty acids
muscle functi
Muscle fiber EOA
type Physical POA Controls
Irina V Astratenkova Æ Antonina I Komkova
Fig. 1 PPARa intron 7 C allele frequency of 786 Russian athletes
V. A Rogozkin performance. Genotype distribution and C allele fre- Our study als
Sports Genetics Laboratory, St Petersburg Research Institute
and 1,242 controls is shown. C allele frequency in controls was
of Physical Culture, 2 Dynamo Street, 197110, quencies
Fig. in athletes
2 Distribution
Introduction of PPARa 7with intron Cmixed power/endurance
allele amongst male and Finally, as in
16.4%. By comparison, it was 10.8, 20.4 and 27.2% for
St Petersburg, Russia female
activity athletes
were in two event groups and position
in intermediate sedentary controls
between (EOA endur-
E-mail: genoterra@mail.ru Peroxisome proliferator-activated
endurance-oriented receptor
athletes, POA power-oriented a (PPARa)
athletes). is
C allele cation within
predominantly aerobic group (n=491), mixed aerobic and anaer-
Tel.: +7-812-2371936
ance- and
a transcription power-orientedathletes,
factor that athletes,
regulates lipid,being
glucose, similar toIn summar
and
Fax: +7-812-2370461
obic group (n=115), and predominantly anaerobic group (n=180), frequencies in endurance-oriented
energy homeostasis and controls body both men
weight [frequency
and vas-
respectivelyD. M Flavell
(P=0.029
Centre for linear trend)
for Cardiovascular Genetics, Department of Medicine,
controls.
11.6% vs controls (frequency 17.1%); P=0.004]
cular inflammation. PPARa is expressed at high levels in and women variation in th
Royal Free and University College London Medical School,
[frequency 9.0%catabolize
tissues that vs controlsfatty(frequency
acids, 15.6%);
notably P=0.007] were physical perf
liver, skeletal
The Rayne Institute, 5 University Street, muscle, and
significantly heart,
different. and at C
Similarly, lower
allelelevels in other
frequencies weretissues,
signifi-
WC1E 6JF, London, UK including pancreas (Braissant et al. 1996). The level of
cantly higher both in male (frequency 26.7%, P=0.0006) and
muscle fiber
expression of PPARa is higher in type I (slow-twitch)
Ekaterina V Lyubaeva Æ P. P Tarakin Æ B. S Shenkman female
than power-oriented athletes (frequency
in type II (fast-twitch) 28.6%,(Russel
muscle fibers P= 0.0033)
et al.
important imp
A. B Vdovina Æ Aleksei I Netreba Æ Daniil V Popov
O. L Vinogradova compared to controls
2003). function in bo
SSC RF Institute for Biomedical Problems, 76A Khoroshevskoe Endurance training increases the use of non-plasma
Chaussee, 123007, Moscow, Russia fatty acids and may enhance skeletal muscle oxidative
H. E Montgomery
Studies to
capacity bydate suggest
PPARa that the C
regulation ofallele
geneseems asso-
expression
(Russel et al. 2003; Horowitz et al. 2000). PPARa reg-
Institute for Human Health and Performance, University College ciated with reduced PPARa expression or function.
London, N19 5LW, London, UK ulates the expression of genes encoding several key References
Hum Genet (2009) 126:751–761
DOI 10.1007/s00439-009-0728-4
ORIGINAL INVESTIGATION
The combined impact of metabolic gene polymorphisms on elite

endurance athlete status and related phenotypes
Ildus I. Ahmetov · Alun G. Williams · Daniil V. Popov · Ekaterina V. Lyubaeva ·
Albina M. Hakimullina · Olga N. Fedotovskaya · Irina A. Mozhayskaya ·
Olga L. Vinogradova · Irina V. Astratenkova · Hugh E. Montgomery · Viktor A. Rogozkin
Received: 3 December 2008 / Accepted: 25 July 2009 / Published online: 4 August 2009
1423 atletas rusos y 1132 controles fueron genotipados para 15 polimorfismos
© Springer-Verlag 2009
Abstract Endurance performance is a complex pheno- 1,132 controls were genotyped for 15 gene polymorphisms,
type subject to the inXuence of both environmental and of which most were previously reported to be associated
genetic factors. Although the last decade has seen a variety with athlete status or related intermediate phenotypes. Mus-
of speciWc genetic factors proposed, many in metabolic cle Wber composition of m. vastus lateralis in 45 healthy
pathways, each is likely to make a limited contribution to men was determined by immunohistochemistry. Maximal
an ‘elite’ phenotype: it seems more likely that such status oxygen consumption of 50 male rowers of national compet-
depends on the simultaneous presence of multiple such itive standard was determined during an incremental test to
variants. The aim of the study was to investigate individu- exhaustion on a rowing ergometer. Ten ‘endurance alleles’
ally and in combination the association of common meta- (NFATC4 Gly160, PPARA rs4253778 G, PPARD
bolic gene polymorphisms with endurance athlete status, rs2016520 C, PPARGC1A Gly482, PPARGC1B 203Pro,
the proportion of slow-twitch muscle Wbers and maximal PPP3R1 promoter 5I, TFAM 12Thr, UCP2 55Val, UCP3
oxygen consumption. A total of 1,423 Russian athletes and rs1800849 T and VEGFA rs2010963 C) were Wrst identiWed
showing discrete associations with elite endurance athlete
status. Next, to assess the combined impact of all 10 gene
Electronic supplementary material The online version of this polymorphisms, all athletes were classiWed according to the
article (doi:10.1007/s00439-009-0728-4) contains supplementary number of ‘endurance’ alleles they possessed. The propor-
material, which is available to authorized users.
tion of subjects with a high (¸9) number of ‘endurance’
I. I. Ahmetov (&) · D. V. Popov · E. V. Lyubaeva · alleles was greater in the best endurance athletes compared
O. L. Vinogradova with controls (85.7 vs. 37.8%, P = 7.6 £ 10¡6). The num-
Laboratory of Muscle Performance, ber of ‘endurance’ alleles was shown to be positively corre-
SSC RF Institute for Biomedical Problems of the Russian
Academy of Sciences, 76A Khoroshevskoe chaussee,
lated (r = 0.50; P = 4.0 £ 10¡4) with the proportion of
123007 Moscow, Russia fatigue-resistant slow-twitch Wbers, and with maximal oxy-
e-mail: genoterra@mail.ru gen consumption (r = 0.46; P = 7.0 £ 10¡4). These data
suggest that the likelihood of becoming an elite endurance
I. I. Ahmetov · A. M. Hakimullina · O. N. Fedotovskaya ·
I. A. Mozhayskaya · I. V. Astratenkova · V. A. Rogozkin
athlete depends on the carriage of a high number of endur-
Sports Genetics Laboratory, ance-related alleles.
St Petersburg Research Institute of Physical Culture,
56 Ligovsky Avenue, 191040 St Petersburg, Russia
Introduction
A. G. Williams
Hum Genet (2009) 126:751–761
Table 1 Candidate genes for endurance performance; their full names, functions of gene products, associated phenotypes and interactions
Gene Full name Functions, associated phenotypes and interactions
ACE Angiotensin I-converting enzyme Regulates circulatory homeostasis through the synthesis of vasoconstrictor angiotensin II and the
degradation of vasodilator kinins (Dzau 1988)
AMPD1 Adenosine monophosphate deaminase 1 Regulates muscle energy metabolism by catalyzing the deamination of adenosine monophosphate to
inosine monophosphate (Lowenstein 1972; Rico-Sanz et al. 2003)
HIF1A Hypoxia-inducible factor 1, !-subunit Regulates the transcription of numerous genes in response to hypoxic stimuli. Genes responsive to HIF1
are involved in the processes of erythropoiesis, angiogenesis, and metabolism and include those encod-
ing erythropoietin, VEGF, PPAR! and glycolytic enzymes (Semenza 2000; Narravula and Colgan 2001)
NFATC4 Nuclear factor of activated T cells, cytoplasmic, Regulates cardiac hypertrophy, glucose and lipid metabolism, expression of the skeletal myosin heavy
calcineurin-dependent 4 chain genes; regulates expression of PPARG (Allen et al. 2001; Poirier et al. 2003; Yang et al. 2006)
PPARA Peroxisome proliferator-activated receptor ! Regulates liver, heart and skeletal muscle lipid metabolism, glucose homeostasis, mitochondrial
biogenesis, cardiac hypertrophy, expression of UCP2 and UCP3 genes (Lefebvre et al. 2006)
PPARD Peroxisome proliferator-activated receptor " Regulates fatty acid #-oxidation, glucose utilization, mitochondrial biogenesis, angiogenesis, muscle Wber
type, expression of PPARGC1A, UCP2, UCP3 and VEGFA genes (Wang et al. 2004, 2006)
PPARG Peroxisome proliferator-activated receptor $ Plays a critical physiological role as a central transcriptional regulator of adipogenic and lipogenic
programs, insulin sensitivity and glucose homeostasis (Semple et al. 2006)
PPARGC1A Peroxisome proliferator-activated receptor $ Regulates fatty acid oxidation, glucose utilization, mitochondrial biogenesis, thermogenesis, angiogenesis,
coactivator 1-! formation of muscle Wbers; co-activates PPAR!, PPAR"; regulates TFAM and VEGFA expression (Lin
et al. 2002; St-Pierre et al. 2003)
PPARGC1B Peroxisome proliferator-activated receptor $ Regulates fatty acid oxidation, mitochondrial biogenesis, formation of muscle Wbers; co-activates PPAR!
coactivator 1 # and PPAR$ (St-Pierre et al. 2003; Arany et al. 2007; Ling et al. 2007)
PPP3R1 Protein phosphatase 3, regulatory subunit B, Confers calcium sensitivity, dephosphorylates and activates NFATC4. Regulates skeletal muscle and heart
alpha isoform (calcineurin subunit B) metabolism/hypertrophy, expression of HIF1A, PPARA, PPARD, PPARGC1A (Chin et al. 1998; Tang
et al. 2005; Long et al. 2007)
TFAM Mitochondrial transcription factor A Involved in mitochondrial transcription regulation, proliferation of mitochondria and mitochondrial
biogenesis (Ekstrand et al. 2004; Alvarez et al. 2008)
UCP2 Uncoupling protein 2 Uncouples oxidative phosphorylation from ATP synthesis; regulates lipid metabolism and energy
expenditure (Buemann et al. 2001; Brand and Esteves 2005)
UCP3 Uncoupling protein 3 Uncouples oxidative phosphorylation from ATP synthesis; regulates lipid metabolism and energy expen-
diture, transports fatty acid anions out of mitochondria (Halsall et al. 2001; Brand and Esteves 2005)
VEGFA Vascular-endothelial growth factor A Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth; expression of VEGFA is
regulated by HIF1 and calcineurin/NFAT signaling (Ferrara 2001; Prior et al. 2006)
123
753
Hum Genet (2009) 126:751–761
We also examined the c

polymorphisms on the two
types we assessed, namely
muscle Wbers in m. vastus
healthy men (n = 45) and m
rowers of the national
55.7 § 0.9 ml/min/kg; n = 5
alleles positively correlated
twitch Wbers (r = 0.50; P =
relation). For men with high
(n = 26) compared with tho
ance’ alleles (n = 19), there
twitch Wbers in the m. vas
43.8 § 2.2%; P = 1.0 £ 10
area occupied by those Wber
The maximal oxygen co
genotype-dependent. We o
Fig. 1 The combined impact of the 10 gene polymorphisms. The per- (r = 0.46; P = 7.0 £ 10¡4)
centage of subjects with high (¸9) number of ‘endurance’ alleles is letes and their carriage o
shown. StratiWcation of athletes was done by endurance/power orien- Those rowers having high
tation and competitive standard. *SigniWcant diVerence (P < 0.05)
from controls by !2 test. The proportion of subjects with a high number (n = 25; VO2max 58.6 § 1
of ‘endurance’ alleles was signiWcantly larger in the mixed group (non- cantly higher maximal ox
elite: 45.6% (n = 193), P = 0.038; sub-elite: 62.9% (n = 35), P = 0.0026; counterparts with low num
elite: 60.0% (n = 20), P = 0.042), in the short-endurance group [non- 25; VO2max 52.8 § 1.0 ml/m
elite: 46.2% (n = 39), P = 0.28; sub-elite: 60.0% (n = 60), P = 5.6 £ 10¡4;
Population and types of injuries in duplicate, and contained 50 ng of each individual’s DNA;
Data were collected on injuries suffered by 73 elite soccer 6.25 μL TaqMan Universal Master Mix (AB); 0.25 μL
players from Futbol Club Barcelona (Barcelona, Catalunya, primers and probes (AB) and water for a final volume of
Spain) over the course of three consecutive soccer seasons. 12.5 μL. Real-time PCR was performed on an ABIPrism
All the players included in the study, either from the first 7500 Sequence Detection System (AB) using the following
(n = 49) and the second team (n = 26) lived within 30 km of conditions: 50°C for 2 minutes, 95°C for 10 minutes, and
the training field, and were thus subjected to the same 40 cycles of amplification (95°C for 15 seconds and 60°C
climate and environmental conditions. All the players for 1 minute). For each cycle, the software determined the
undertook similar amount of work, followed similar diet fluorescent signal from the VIC- or FAM- labeled probe.
(data not available), and took the same ergogenic aids. The
training field, the playing fields and the injury prevention Statistical analyses
protocols were also identical for all the players. The treat- Descriptive statistics of the main demographic variables
ment protocol for each type of injury, including medication of the studied population (mean, standard deviation, or
and physical therapy, was the same for all the players, and median, range, for continuous data, and frequency tables
all treatment was supervised by the same medical team. for specific data) was calculated. Frequency tables were
Given the high qualification level of the study popula- used for the distribution of the SNPs for the different
tion (73 male professional soccer players from the same genes evaluated.
football team) and based on the sample size (n = 242) of
the NCSMTIs encountered, we decided to study the most Table 1 Characteristics and functions of the SNPs
common injury in each tissue group, i.e. hamstring injuries included in the study
for muscle injuries, patellar tendon injuries for tendon in- Gene Related function rsNCBI
juries, and medial collateral ligament injuries for ligament ELN [22] Tissue repair rs2289360
injuries. Data on injuries were collected in accordance
TTN [24] Muscle assembly rs2742327
with the Union of European Football Associations (UEFA)
protocol [30]. Ultrasound and magnetic resonance im- Force transmission
aging scans were used to morphologically classify the in- SOX15 [25] Skeletal muscle regeneration rs4227
juries by anatomic region. Injuries were classified as mild, IGF2 [26] Muscle damage rs3213221
moderate or severe [31] according to the number of days CCL2 [27] Response to muscle damage rs2857656
that a player needed to be absent from training and/or TNC [10] Tendinopathy rs2104772
competition [32,33]: mild, 1–15 days; moderate, 16–30
COL1A1 [28] Ligament ruptures rs1800012
days; and severe, more than 30 days. A mild lesion presents
minimal tissue damage (up to 25%), a moderate injury in- COL5A1 [28] Ligament ruptures rs12722
volves 50% of the tissue and, finally, in a serious injury Tendinopathy
more than 50% of the tissue is involved. Recovery time was The numbers in brackets are the relevant references.
Musculoskeletal Disorders 2013, 14:221

Pruna et al. BMC Musculoskeletal Disorders 2013, 14:221 Page 5 of 7
http://www.biomedcentral.com/1471-2474/14/221
A Degree
B Degree
IGF2 p=0.034 mild CCL2 p=0.026 mild
moderate moderate
severe severe
Number of Injuries
Number of Injuries
GG CC/CG
C
Degree
COL5A1 p=0.08 mild
moderate
severe
Number of Injuries
Figure 1 Relation between muscle injuries and degree. Association of IGF2, CCL2 and COL5A1 to degree of muscle injury. A) Individuals with
the heterozygous variant of IGF2 suffered less severe injuries. B) Carriers of the CCL2 C allele experienced less severe injuries. C) Carriers of the
COL5A1 T allele showed a tendency towards more severe injuries (see Table 3).
SNPs in CCL2 have been related to markers of muscle must be present [55]. This is particularly evident in studies
injury, such as creatine kinase and myoglobin levels and of tendinopathy, where the presence of the C allele has
muscle pain [27]. been associated with asymptomatic patients [12,56].
Individuals with the COL5A1 CC genotype showed a Musculoskeletal
Although dealing with extremely Disorders 2013,
high qualification ath- 14:221
tendency towards less severe muscle injuries than those letes, we acknowledge that the size of our cohort is
with the TC genotype (Table 3). COL5A1 encodes the α1 relatively small, and our results should be therefore
Figure 1 Relation between muscle injuries and degree. Association of IGF2, CCL2 and COL5A1 to degree of muscle injury. A) Individuals with
the heterozygous variant of IGF2 suffered less severe injuries. B) Carriers of the CCL2 C allele experienced less severe injuries. C) Carriers of the
COL5A1 T allele showed a tendency towards more severe injuries (see Table 3).
SNPs in CCL2 have been related to markers of muscle must be present [55]. This is particularly evident in studies
injury, such as creatine kinase and myoglobin levels and of tendinopathy, where the presence of the C allele has
muscle pain [27]. been associated with asymptomatic patients [12,56].
Individuals with the COL5A1 CC genotype showed a Although dealing with extremely high qualification ath-
tendency towards less severe muscle injuries than those letes, we acknowledge that the size of our cohort is
with the TC genotype (Table 3). COL5A1 encodes the α1 relatively small, and our results should be therefore
chain of collagen type V, which forms part of the extracel- interpreted with caution. Nevertheless, the SNPs identified
lular matrix of the skeletal muscles [54]. These COL5A1 in the ELN gene showed a significant statistical association
molecules connect with collagen type I fibers in non- with the degree of ligament injuries (p = 0.009) and with
cartilage connective tissue, modulating fibrillogenesis. recovery time (p = 0.043). ELN, a self-assembling extracel-
However, for this process to be successful, both C alleles lular matrix protein, is the major source of tissue elasticity
A Degree
B
p=0.009
ELN mild p=0.043
moderate
severe
Number of Injuries
Figure 2 ELN related to ligament injuries. Relation of ELN with degree of injury and recovery time. A) Individuals without the G allele suffered
more severe injuries (see Table 3). B) Carriers of the G allele exhibited had faster recovery times.
Musculoskeletal Disorders 2013, 14:221

JOURNAL OF SPORTS SCIENCES, 2016
http://dx.doi.org/10.1080/02640414.2016.1215494
Tour de France Champions born or made: where do we take the genetics

of performance?
Colin N. Moran a
and Yannis P. Pitsiladisb
Physiology, Exercise and Nutrition Research Group, University of Stirling, Stirling, Scotland; bFIMS Reference Collaborating Centre of Sports
a
Medicine for Anti-Doping Research, University of Brighton, Eastbourne, England
ABSTRACT ARTICLE HISTORY

Cyclists in the Tour de France are endurance specialists. Twin and family studies have shown that Accepted 15 July 2016
approximately 50% of the variance in a number of performance-related phenotypes (whether measured
KEYWORDS
at baseline, i.e., natural talent, or in response to training) including those important to cycling can be Genetics; epigenetics;
explained by genetic variation. Research into the specific genetic variants that are responsible has cyclists; elite athlete cohorts;
identified over 200 genes containing common genetic variants involved in the genetic predisposition to PowerGene; GAMES;
physical performance. However, typically these explain only a small portion of the variance, perhaps Athlome
1–2% and collectively they rarely explain anything approaching the 50% of the variance identified in
y of Leeds] at 02:24 07 August 2016
the twin and family studies. Thus, there is a gap in our understanding of the relationship between
heritability and performance. This gap may be bridged by investigation of rare variants or epigenetic
variation or by altering study designs through increased collaborations to pool existing cohorts
together. Initial findings from such efforts show promising results. This mini-review will touch on the
genetics and epigenetics of sporting performance, how they relate to cyclists in the Tour de France and
where best future efforts may be directed as well as discuss some preliminary research findings.
Introduction terrain, they have to cover all three types of terrain. Their
characteristics are reviewed in Lucia, Hoyos, and Chicharro
Since at least the time of the Ancient Greeks humans have
(2001). In summary, typically they will all have high maximal
challenged each other in competitive performance tasks.
Table 1. Candidate gene association studies comparing cyclists to controls showing study characteristics and findings.
Ethnicity & Athletes
Gene Variant Study design Athletes Gender (cyclists) Controls Association (reference)
ACE rs4646994 Case–control Professional cyclists, long- Spanish males 60 (25) 400 I-allele over-represented in athletes compared to controls (Alvarez et al.,
(intron 16 indel) distance runners and 2000).
handball players
Case–control Professional cyclists and Spanish males 77 (50) 119 DD genotype over-represented in cyclists compared to controls or runners.
Olympic-class endurance D-allele over-represented in cyclists compared to runners (Lucía et al.,
runners 2005).
Case–control Mixed endurance and power or Iranian males 156 (37) 163 D-allele over-represented in cyclists compared to controls (Shahmoradi,
sprint sports Ahmadalipour, & Salehi, 2014).
Case–control Professional cyclists, Olympic- Spanish males 141 (50) 123 II under-represented in rowers compared to whole cohort (Muniesa et al.,
class endurance runners and 2010).
World class rowers
Case–control Endurance, power and mixed Lithuanian males 193 (12) 250 DD genotype over-represented in endurance compared to power athletes. DD
Quantitative muscle power athletes and females genotype lower power than II genotype (Ginevičienė, Pranckevičienė,
Milašius, & Kučinskas, 2010).
ACTN3 rs1815739 Case–control Professional cyclists and Spanish males 102 (50) 123 No association with endurance (Lucia et al., 2006).
(p.R577X) _ 2max data
Quantitative VO Olympic-class endurance
runners
Case–control Endurance-oriented athletes Russian males 456 (34) 1211 C-allele (577X) under-represented in endurance athletes (Ahmetov et al.,
including road cyclists and females 2010).
Case–control Professional cyclists, Olympic- Spanish males 141 (50) 123 No association with endurance (Muniesa et al., 2010).
class endurance runners and
World class rowers
Case–control Endurance, power and mixed Lithuanian males 193 (12) 250 No association with athlete group or power (Ginevičienė et al., 2010).
Quantitative muscle power athletes and females
ADRB3 rs4994 Case–control Professional cyclists, Olympic- Spanish males 153 (50) 100 C-allele (64R) over-represented in endurance athletes compared to controls
(p.W64R) class endurance runners and (Santiago et al., 2011).
power athletes
AGT rs699 Case–control Professional cyclists, Olympic- Spanish males 163 (50) 119 No association with endurance. C-allele (235T) may favour power
(p.M235T) class endurance runners and performance (Gomez-Gallego et al., 2009).
power athletes
Case–control Professional cyclists, long- Spanish males 60 (25) 400 No association with endurance (Alvarez et al., 2000).
distance runners and
handball players
AGTR1 rs12721277 Case–control Professional cyclists, long- Spanish males 60 (25) 400 No association with endurance (Alvarez et al., 2000).
(c.*82G>A) distance runners and
handball players
AMPD1 rs17602729 Case–control Professional cyclists and Spanish males 104 (50) 100 C-allele (45Q) over-represented in endurance athletes although do not have
(p.Q45X) _ 2max data
Quantitative VO Olympic-class endurance higher VO_ 2max (Rubio et al., 2005).
JOURNAL OF SPORTS SCIENCES

runners
World class rowers
Case–control Endurance, power and mixed Lithuanian males 204 (12) 260 TT genotype (45XX) absent from athlete group. T-allele under-represented in
Quantitative muscle power athletes and females power athletes compared to controls. CC genotype associated with muscle
power (Ginevičienė et al., 2014).
CKMM rs8111989 Case–control Professional cyclists and Spanish males 77 (50) 119 No association with endurance (Lucía et al., 2005).
(g.45809208 TC) Olympic-class endurance
runners
World class rowers
(Continued )
3
4
C. N. MORAN AND Y. P. PITSILADIS
Table 1. (Continued).
Ethnicity & Athletes
Gene Variant Study design Athletes Gender (cyclists) Controls Association (reference)
GDF8 rs1805086 Case–control Professional cyclists, Olympic- Spanish males 141 (50) 123 No association with endurance (Muniesa et al., 2010).
(p.K153R) class endurance runners and
World class rowers
HFE rs1799945 (p. Case–control Professional road cyclists with French males 77 (77) 254 G-allele (63D) over-represented in cyclists compared to controls (Deugnier
H63D) hyperferritinemia et al., 2002).
Case–control Professional cyclists and Spanish males 65 (50) 134 G-allele (63D) over-represented in endurance athletes although do not have
_ 2max data
Quantitative VO Olympic-class endurance higher VO_ 2max (Chicharro et al., 2004).
runners
IL6 rs1800795 Case–control Professional cyclists, Olympic- Spanish males 153 (50) 100 No association with endurance. GG genotype and G-allele over-represented in
(c.-174 CG) class endurance runners and power athletes compared to controls or endurance athletes (Ruiz et al.,
power athletes 2010).
IL15RA rs2228059 Case–control Mixed endurance and sprint- European 308 (73: 43 258 A-allele (12N) over-represented in all cyclists compared to controls (Pistilli
(p.N12T) power sports Australian endurance; 30 et al., 2011).
males and sprint-power)
females
MtDNA Haplogroup Case–control Professional cyclists, Olympic- Spanish males 153 (50) 478 V haplogroup over-represented in elite endurance athletes compared to
class endurance runners and controls (Nogales-Gadea et al., 2011).
power athletes
NOS3 rs2070744 Case–control Professional cyclists, Olympic- Spanish males 153 (50) 100 No association with endurance. TT genotype and T-allele over-represented in
(c.-786 CT) class endurance runners and power athletes compared to controls or endurance athletes (Gómez-
power athletes Gallego et al., 2009).
PER3 VNTR (54 bp Case–control Cyclists, runners and Ironman South African 532 (125) 96 PER3(5/5) over-represented in all athletes compared to controls (Kunorozva,
repeat) triathletes males of Stephenson, Rae, & Roden, 2012).
European
descent
PPARA rs4253778 Case–control Endurance, power and mixed Lithuanian males 193 (12) 250 C-allele over-represented in all athletes compared to controls (Ginevičienė
(c.2528G>C) Quantitative muscle power athletes and females et al., 2010).
PPARD rs2016520 Case–control Endurance and power athletes Russian males 1256 (108) 610 C-allele over-represented in endurance athletes (Ahmetov, Astratenkova, &
(c.-87 CT) from a range of sports and females Rogozkin, 2007)
PPARGC1A rs8192678 Case–control Professional cyclists and Spanish males 104 (50) 164 G-allele (482G) predicts exceptional endurance capacity (Lucia et al., 2005).
(p.G482S) _ 2max data
Quantitative VO Olympic-class endurance
runners
World class rowers
Case–control Endurance, power and mixed Lithuanian males 193 (12) 250 482S homozygotes had higher power performance (Ginevičienė et al., 2010).
Quantitative muscle power athletes and females
TFAM rs1937 Case–control Endurance and power athletes Russian 1537 (109) 1113 C-allele (12T) over-represented in endurance athletes (Ahmetov, Popov,
(p.S12T) _ 2max data
Quantitative VO from a range of sports Missina, Vinogradova, & Rogozkin, 2010).
VEGFA rs2010963 Case–control Endurance and power athletes Russian males 670 (110) 1073 C-allele over-represented in endurance athletes (Ahmetov et al., 2008).
(c.-634 CG) _ 2max data
Quantitative VO from a range of sports and females
VEGFR2 rs1870377 Case–control Endurance and power athletes Russian males 471 (11) 603 A-allele (472Q) with endurance-related phenotypes (Ahmetov et al., 2009).
(p.Q472H) _ 2max data
Quantitative VO from a range of sports and females
Banting et al. BMC Genomics (2015) 16:25
DOI 10.1186/s12864-014-1199-0
RESEARCH ARTICLE Open Access
Elite athletes’ genetic predisposition for altered

risk of complex metabolic traits
Lauren K Banting1, Vladimir P Pushkarev2, Pawel Cieszczyk3, Aleksandra Zarebska4, Agnieszka Maciejewska-Karlowska3,
M-arek Sawczuk3, Agata Leońska-Duniec3, Dmitry A Dyatlov2, Evgeniy F Orekhov2, Aleksandr V Degtyarev2,
Yuliya E Pushkareva5, Xu Yan1,6, Ruth Birk7*† and Nir Eynon1,6*†
Abstract
Background: Genetic variants may predispose humans to elevated risk of common metabolic morbidities such
as obesity and Type 2 Diabetes (T2D). Some of these variants have also been shown to influence elite athletic
performance and the response to exercise training. We compared the genotype distribution of five genetic
Single Nucleotide Polymorphisms (SNPs) known to be associated with obesity and obesity co-morbidities
(IGF2BP2 rs4402960, LPL rs320, LPL rs328, KCJN rs5219, and MTHFR rs1801133) between athletes (all male, n = 461;
endurance athletes n = 254, sprint/power athletes n = 207), and controls (all male, n = 544) in Polish and Russian
samples. We also examined the association between these SNPs and the athletes’ competition level (‘elite’ and
‘national’ level). Genotypes were analysed by Single-Base Extension and Real-Time PCR. Multinomial logistic
regression analyses were conducted to assess the association between genotypes and athletic status/competition
level.
Results: IGF2BP2 rs4402960 and LPL rs320 were significantly associated with athletic status; sprint/power athletes
were twice more likely to have the IGF2BP2 rs4402960 risk (T) allele compared to endurance athletes (OR = 2.11,
95% CI = 1.03-4.30, P <0.041), and non-athletic controls were significantly less likely to have the T allele compared
to sprint/power athletes (OR = 0.62, 95% CI =0.43-0.89, P <0.0009). The control group was significantly more likely
to have the LPL rs320 risk (G) allele compared to endurance athletes (OR = 1.26, 95% CI = 1.05-1.52, P <0.013).
Hence, endurance athletes were the “protected” group being significantly (p < 0.05) less likely to have the risk
allele compared to sprint/power athletes (IGF2BP2 rs4402960) and significantly (p < 0.05) less likely to have the risk
allele compared to controls (LPL rs320). The other 3 SNPs did not show significant differences between the study
groups.
Conclusions: Male endurance athletes are less likely to have the metabolic risk alleles of IGF2BP2 rs4402960 and
LPL rs320, compared to sprint/power athletes and controls, respectively. These results suggest that some SNPs
across the human genome have a dual effect and may predispose endurance athletes to reduced risk of
developing metabolic morbidities, whereas sprint/power athletes might be predisposed to elevated risk.
Keywords: Genes, Exercise, Athletes, Obesity, Type 2 diabetes
(n = 2), rowers (n = 13), 1500-5000 m runners (n = 4), ing to the manufacturer’s instructions. In the Russian co-
5000/10 000 m long distance skaters (n = 6), 3000 m hort, Genomic DNA was isolated from buccal epithelium
steeple chase (n = 1), 1500 m swimmers (n = 2) and or peripheral blood, during the years 2011-2013, using the
walkers (n = 4). Athletes classified as sprint/power ath- Diatom™ DNA Prep kit (Cat. # D 1025, IsoGene Lab
letes came from sports including ski-cross/ alpine ski- Ltd, Russia). Genotyping was performed as previously
ing (n = 2), discus throw (n = 1), Greco-roman wrestling described [29]. In the Russian cohort, genotyping of
(n = 10), pole vault (n = 1), 200 m sprint (n = 2), 100 m four SNPs (IGFBP2 rs4402960, KCJN11 rs5219, LPL
sprint (n = 10), 400 m sprint (n = 1), 500 m short rs320 and rs328) was performed by Single-Base
Table 1 Genotype frequency distributions for IGFBP2 rs4402960

Polish (n = 648) Russian (n = 281)
Endurance Sprint/Power Control Endurance Sprint/Power Control
All (N) 108 100 440 70 107 104
TT 10 (9%) 16 (16%) 42 (10%) 4 (6%) 13(12%) 11 (11%)
GT 47 (44%) 40 (40%) 163 (37%) 37 (53%) 58 (54%) 39 (38%)
GG 51 (47%) 44 (44%) 235 (53%) 29 (41%) 36 (34%) 54 (52%)
MAF 0.31 0.36 0.28 0.32 0.39 0.29
HWE-P value 0.987 0.419 0.223 0.208 0.368 0.623
Elite (N) 65 64 - 10 44 -
TT 4 (6%) 14 (22%) 2 (20%) 7 (16%)
GT 28 (43%) 20 (31%) 5 (50%) 22 (50%)
GG 33 (51%) 30 (47%) 3 (30%) 15 (34%)
MAF 0.28 0.38 0.45 0.41
National Level (N) 43 36 60 63 -
TT 6 (14%) 2 (6%) 2 (3%) 6 (10%)
GT 19 (44%) 20 (56%) 32 (53%) 36 (57%)
GG 18 (42%) 14 (39%) 26 (43%) 21 (33%)
MAF 0.36 0.33 0.30 0.38
Note: TT is identified as the risk genotype.
Conclusions: Male endurance athletes are less likely to have the metabolic
risk alleles of IGF2BP2 rs4402960 and LPL rs320, compared to sprint/power
athletes and controls, respectively. These results suggest that some SNPs
across the human genome have a dual effect and may predispose
endurance athletes to reduced risk of developing metabolic morbidities,
whereas sprint/power athletes might be predisposed to elevated risk.
Epigenética
Med. Sci. Sports Exerc., Vol. 43, No. 5, pp. 743–752, 2011

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Dr. Jorge Cancino L. PhD.

Introduction gene [3,4]. The ACE insertion/deletion (ACE I/D, rs1799752)

PLOS ONE | www.plosone.org 4 January 2013 | Volume 8 | Issue 1 | e54685

PLOS ONE | www.plosone.org 5 January 2013 | Volume 8 | Issue 1 | e54685

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PLOS ONE | www.plosone.org 7 January 2013 | Volume 8 | Issue 1 | e54685

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ACTN3: More than Just a Gene for

Pickering and Kiely 1

Study Method Sample characteristics Main outcome

Frontiers in Physiology | www.frontiersin.org 5 December 2017 | Volume 8 | Article 1080

FIGURE 1 - Contribution of genetic factors to performance-relevant quantitative traits.

Percent variance explained 40

C 2016 The Authors. The Journal of Physiology ⃝

J Physiol 595.9 (2017) pp 2931–2939

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Ildus I Ahmetov Æ Irina A Mozhayskaya

PPARa gene variation and physical performance in Russian athletes

The combined impact of metabolic gene polymorphisms on elite

We also examined the c

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Musculoskeletal Disorders 2013, 14:221

Tour de France Champions born or made: where do we take the genetics

Medicine for Anti-Doping Research, University of Brighton, Eastbourne, England

ABSTRACT ARTICLE HISTORY

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RESEARCH ARTICLE Open Access

Elite athletes’ genetic predisposition for altered

Table 1 Genotype frequency distributions for IGFBP2 rs4402960

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