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Polymorphisms in TICAM2 and IL1B are associated with TB
Noémi Borsay Hall1, Robert P Igo1, LaShaunda L Malone2
1Dept. of Epidemiology & Biostatistics, Case Western Reserve Univ., Cleveland, OH.
Genes and Immunity
|December 19, 2014
Summary
Genetic factors influence tuberculosis (TB) risk and resistance. This study identified specific gene variations linked to TB susceptibility and distinct genetic markers associated with resistance to Mycobacterium tuberculosis (Mtb) infection.
Area of Science:
- Immunogenetics
- Tuberculosis Research
- Human Genetics
Background:
- Human genetic susceptibility to tuberculosis (TB) is recognized, but comprehensive analyses of immune genes, age-specific effects, and genetic resistance to Mycobacterium tuberculosis (Mtb) are limited.
- Resistance to Mtb infection (RSTRs), defined by persistent negative tuberculin skin tests, may involve different genetic factors than TB disease.
Purpose of the Study:
- To investigate genetic influences on TB susceptibility and Mtb infection resistance by examining candidate genes involved in immune responses.
- To identify specific single-nucleotide polymorphisms (SNPs) associated with TB disease and Mtb resistance in a Ugandan household contact study.
- To explore age-genotype interactions in relation to TB susceptibility.
Main Methods:
- Genotyped 546 haplotype-tagging SNPs in 835 individuals from 481 families in a Ugandan household contact study.
- Classified individuals into TB cases (28.7%), RSTRs (10.5%), and latent Mtb infection (60.8%).
- Performed association analyses to identify SNPs linked to TB and RSTR phenotypes, including age-genotype interaction analyses.
Main Results:
- Identified significant associations between SNPs in TICAM2 (P = 3.6 × 10(-6)) and IL1B (P = 4.3 × 10(-5)) with TB. Multiple SNPs in IL4 and TOLLIP were also associated with TB (P < 0.05).
- Found suggestive associations between SNPs in IL18 and TLR6 with TB in children aged ⩽ 10 years (P = 2.9 × 10(-3)).
- Discovered associations between RSTR and SNPs in NOD2, SLC6A3, and TLR4 (nominal P < 0.05), which were not associated with TB, indicating distinct genetic influences. Reported novel associations between TICAM2 polymorphisms and TB, and IL18 and pediatric TB.
Conclusions:
- Distinct genetic factors influence TB disease susceptibility versus Mtb infection resistance.
- Specific gene polymorphisms in TICAM2, IL1B, IL4, and TOLLIP are associated with TB.
- IL18 and TLR6 SNPs may play a role in pediatric TB, and NOD2, SLC6A3, and TLR4 SNPs are linked to Mtb resistance.
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