TB

 Mycobacterium
tuberculosis
 major challenge to
global public health
TB

 higher risk for active TB:

Elderly

Infants

People with weakened immune systems

TB
 Risk of contracting TB increases if you:
 Frequent contact with persons having TB
 Have poor nutrition
 Live in crowded unsanitary conditions

rates vary dramatically by area of residence and

socioeconomic status
TB

 1/3rd of the world’s population is

infected, but

 Only 10% of world's population get

sick with TB after being exposed
 1 in 10
The Question
 Why 90% are protected
 What's the difference between them?"

 Some people seem to have a particular

genetic heritage that makes them
naturally resistant to TB infection
TB
 Still, TB : major global health problem,
particularly in developing countries

 It sickens 8 million additional people

each year

 of which 2 million will die

TB

 If scientists could find

out what is going on in
the bodies of the other
nine people …….
TB
 what is going on in the bodies of the
other nine people

 Is approached from
GENETICS
TB
 A genetic region has been discovered to be
associated with clinical TB

 People with at least one high-risk copy of

this genetic region are ten times more likely
to develop TB than normal

 The genetic region contains a gene,

SLC11A1
TB

 1998: for the first time, relation

between

 SLC11A1 polymorphisms and TB

susceptibility reported in population
from West Africa
TB

SLC11A1
solute carrier
family 11
TB
SLC11A1 gene
 Encodes the Natural Resistance Associated
Macrophage Protein 1 (NRAMP1)

 multiple effects on macrophage activation

 Macrophage-specific membrane transport
function

 role in host immune response against

infections
 SLC11A1 gene
Rev iew: Inf ectious Disease
Comparison: 01 TB
Outcome: 01 SLC11A1

Study case control OR (random) Weight OR (random)

or sub-category n/N n/N 95% CI % 95% CI

Fitness 2004 103/464 352/1556 12.10 0.98 [0.76, 1.25]

Awomoy i 2002 109/658 81/648 10.86 1.39 [1.02, 1.90]
Bellamy 1998 151/802 115/820 11.78 1.42 [1.09, 1.85]
Soborg 2007 99/486 102/680 10.97 1.45 [1.07, 1.97]
Leung 2007 78/556 71/564 10.17 1.13 [0.80, 1.60]
Hsu 2006c 30/220 18/156 5.79 1.21 [0.65, 2.26]
Gao 2000 129/534 59/404 10.27 1.86 [1.33, 2.62]
Hsu 2006d 19/202 4/176 2.52 4.46 [1.49, 13.39]
Soborg 2002 22/94 121/352 7.06 0.58 [0.34, 0.99]
Ates 2008 38/224 28/160 6.90 0.96 [0.56, 1.65]
Ma 2002e 60/202 42/216 8.20 1.75 [1.11, 2.75]
Ma 2002f 8/24 42/216 3.39 2.07 [0.83, 5.16]

Total (95% CI) 4466 5948 100.00 1.31 [1.08, 1.59]

Total ev ents: 846 (case), 1035 (control)
Test f or heterogeneity : Chi² = 28.78, df = 11 (P = 0.002), I² = 61.8%
Test f or ov erall ef f ect: Z = 2.78 (P = 0.005)

0.1 0.2 0.5 1 2 5 10

increased decreased
SLC11A1 gene

 Population  Determine
 Sub-group analysis  pooled effects
for each
 Determine subgroup
 Weight % of each study  effects in the
 Tests for heterogeneity three populations
 Z-test 

 Analysis model
 Subgroup Analysis

Rev iew: Inf ectious Disease

Comparison: 01 TB
Outcome: 01 SLC11A1

Study case control OR (f ixed) Weight OR (f ixed)

or sub-category n/N n/N 95% CI % 95% CI

Fitness 2004 103/464 352/1556 35.55 0.98 [0.76, 1.25]

Awomoy i 2002 109/658 81/648 19.24 1.39 [1.02, 1.90]
Bellamy 1998 151/802 115/820 26.08 1.42 [1.09, 1.85]
Soborg 2007 99/486 102/680 19.13 1.45 [1.07, 1.97]

Total (95% CI) 2410 3704 100.00 1.26 [1.10, 1.45]

Total ev ents: 462 (case), 650 (control)
Test f or heterogeneity : Chi² = 6.04, df = 3 (P = 0.11), I² = 50.3%
Test f or ov erall ef f ect: Z = 3.30 (P = 0.0010)

0.5 0.7 1 1.5 2

increased decreased

Africans
 Subgroup Analysis

Rev iew: Inf ectious Disease

Comparison: 01 TB
Outcome: 01 SLC11A1

Study case control OR (random) Weight OR (random)

or sub-category n/N n/N 95% CI % 95% CI

Leung 2007 78/556 71/564 33.35 1.13 [0.80, 1.60]

Hsu 2006c 30/220 18/156 22.11 1.21 [0.65, 2.26]
Gao 2000 129/534 59/404 33.58 1.86 [1.33, 2.62]
Hsu 2006d 19/202 4/176 10.96 4.46 [1.49, 13.39]

Total (95% CI) 1512 1300 100.00 1.58 [1.04, 2.41]

Total ev ents: 256 (case), 152 (control)
Test f or heterogeneity : Chi² = 8.36, df = 3 (P = 0.04), I² = 64.1%
Test f or ov erall ef f ect: Z = 2.12 (P = 0.03)

0.1 0.2 0.5 1 2 5 10

increased decreased

Asians
 Subgroup Analysis

Rev iew: Inf ectious Disease

Comparison: 01 TB
Outcome: 01 SLC11A1

Study case control OR (random) Weight OR (random)

or sub-category n/N n/N 95% CI % 95% CI

Soborg 2002 22/94 121/352 26.75 0.58 [0.34, 0.99]

Ates 2008 38/224 28/160 26.50 0.96 [0.56, 1.65]
Ma 2002e 60/202 42/216 28.44 1.75 [1.11, 2.75]
Ma 2002f 8/24 42/216 18.31 2.07 [0.83, 5.16]

Total (95% CI) 544 944 100.00 1.15 [0.65, 2.03]

Total ev ents: 128 (case), 233 (control)
Test f or heterogeneity : Chi² = 11.72, df = 3 (P = 0.008), I² = 74.4%
Test f or ov erall ef f ect: Z = 0.48 (P = 0.63)

0.1 0.2 0.5 1 2 5 10

increased decreased

Westerns