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Mycobacterium Tuberculosis: Major Challenge To Global Public Health

The document discusses tuberculosis (TB) and the SLC11A1 gene. It notes that while 1/3 of the world's population is infected with TB, only 10% get sick after exposure. There may be genetic factors influencing susceptibility. The SLC11A1 gene encodes a protein involved in the immune response against infections. Studies have found associations between polymorphisms in the SLC11A1 gene and susceptibility to developing TB. Subgroup analyses found the association was significant for African and Asian populations but not European populations, suggesting genetic factors influencing susceptibility may differ between populations.

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71 views19 pages

Mycobacterium Tuberculosis: Major Challenge To Global Public Health

The document discusses tuberculosis (TB) and the SLC11A1 gene. It notes that while 1/3 of the world's population is infected with TB, only 10% get sick after exposure. There may be genetic factors influencing susceptibility. The SLC11A1 gene encodes a protein involved in the immune response against infections. Studies have found associations between polymorphisms in the SLC11A1 gene and susceptibility to developing TB. Subgroup analyses found the association was significant for African and Asian populations but not European populations, suggesting genetic factors influencing susceptibility may differ between populations.

Uploaded by

rnrmmanphd
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPT, PDF, TXT or read online on Scribd
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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

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