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Polymorphisms in TICAM2 and IL1B are associated with TB

BACKGROUND: Human genetic susceptibility for tuberculosis (TB) has been demonstrated by several studies, but few have examined multiple innate and adaptive immunity genes comprehensively, age-specific effects, and/or resistance to Mycobacterium tuberculosis (Mtb) infection (RSTR). We hypothesized th...

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Autores principales: Hall, Noémi Borsay, Igo, Robert P., Malone, LaShaunda L., Truitt, Barbara, Schnell, Audrey, Tao, Li, Okware, Brenda, Nsereko, Mary, Chervenak, Keith, Lancioni, Christina, Hawn, Thomas R., Mayanja-Kizza, Harriet, Joloba, Moses L., Boom, W. Henry, Stein, Catherine M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352113/
https://www.ncbi.nlm.nih.gov/pubmed/25521228
http://dx.doi.org/10.1038/gene.2014.77
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author Hall, Noémi Borsay
Igo, Robert P.
Malone, LaShaunda L.
Truitt, Barbara
Schnell, Audrey
Tao, Li
Okware, Brenda
Nsereko, Mary
Chervenak, Keith
Lancioni, Christina
Hawn, Thomas R.
Mayanja-Kizza, Harriet
Joloba, Moses L.
Boom, W. Henry
Stein, Catherine M.
author_facet Hall, Noémi Borsay
Igo, Robert P.
Malone, LaShaunda L.
Truitt, Barbara
Schnell, Audrey
Tao, Li
Okware, Brenda
Nsereko, Mary
Chervenak, Keith
Lancioni, Christina
Hawn, Thomas R.
Mayanja-Kizza, Harriet
Joloba, Moses L.
Boom, W. Henry
Stein, Catherine M.
author_sort Hall, Noémi Borsay
collection PubMed
description BACKGROUND: Human genetic susceptibility for tuberculosis (TB) has been demonstrated by several studies, but few have examined multiple innate and adaptive immunity genes comprehensively, age-specific effects, and/or resistance to Mycobacterium tuberculosis (Mtb) infection (RSTR). We hypothesized that RSTR, defined by a persistently negative tuberculin skin test, may have different genetic influences than Mtb disease. METHODS: We examined 29 candidate genes in pathways that mediate immune responses to Mtb in subjects in a household contact study in Kampala, Uganda. We genotyped 546 haplotype-tagging single nucleotide polymorphisms (SNPs) in 835 individuals from 481 families; 28.7% had TB, 10.5% were RSTR, and the remaining 60.8% had latent Mtb infection. RESULTS: Among our most significant findings were SNPs in TICAM2 (p=3.6×10(−6)) and IL1B (p=4.3×10(−5)) associated with TB. Multiple SNPs in IL4 and TOLLIP were associated with TB (p<0.05). Age-genotype interaction analysis revealed SNPs in IL18 and TLR6 that were suggestively associated with TB in children ≤ 10 years old (p=2.9×10(−3)). By contrast, RSTR was associated with SNPs in NOD2, SLC6A3 and TLR4 (nominal p < 0.05); these genes were not associated with TB, suggesting distinct genetic influences. CONCLUSIONS: We report the first association between TICAM2 polymorphisms and TB, and between IL18 and pediatric TB.
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spelling pubmed-43521132015-09-01 Polymorphisms in TICAM2 and IL1B are associated with TB Hall, Noémi Borsay Igo, Robert P. Malone, LaShaunda L. Truitt, Barbara Schnell, Audrey Tao, Li Okware, Brenda Nsereko, Mary Chervenak, Keith Lancioni, Christina Hawn, Thomas R. Mayanja-Kizza, Harriet Joloba, Moses L. Boom, W. Henry Stein, Catherine M. Genes Immun Article BACKGROUND: Human genetic susceptibility for tuberculosis (TB) has been demonstrated by several studies, but few have examined multiple innate and adaptive immunity genes comprehensively, age-specific effects, and/or resistance to Mycobacterium tuberculosis (Mtb) infection (RSTR). We hypothesized that RSTR, defined by a persistently negative tuberculin skin test, may have different genetic influences than Mtb disease. METHODS: We examined 29 candidate genes in pathways that mediate immune responses to Mtb in subjects in a household contact study in Kampala, Uganda. We genotyped 546 haplotype-tagging single nucleotide polymorphisms (SNPs) in 835 individuals from 481 families; 28.7% had TB, 10.5% were RSTR, and the remaining 60.8% had latent Mtb infection. RESULTS: Among our most significant findings were SNPs in TICAM2 (p=3.6×10(−6)) and IL1B (p=4.3×10(−5)) associated with TB. Multiple SNPs in IL4 and TOLLIP were associated with TB (p<0.05). Age-genotype interaction analysis revealed SNPs in IL18 and TLR6 that were suggestively associated with TB in children ≤ 10 years old (p=2.9×10(−3)). By contrast, RSTR was associated with SNPs in NOD2, SLC6A3 and TLR4 (nominal p < 0.05); these genes were not associated with TB, suggesting distinct genetic influences. CONCLUSIONS: We report the first association between TICAM2 polymorphisms and TB, and between IL18 and pediatric TB. 2014-12-18 2015-03 /pmc/articles/PMC4352113/ /pubmed/25521228 http://dx.doi.org/10.1038/gene.2014.77 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Hall, Noémi Borsay
Igo, Robert P.
Malone, LaShaunda L.
Truitt, Barbara
Schnell, Audrey
Tao, Li
Okware, Brenda
Nsereko, Mary
Chervenak, Keith
Lancioni, Christina
Hawn, Thomas R.
Mayanja-Kizza, Harriet
Joloba, Moses L.
Boom, W. Henry
Stein, Catherine M.
Polymorphisms in TICAM2 and IL1B are associated with TB
title Polymorphisms in TICAM2 and IL1B are associated with TB
title_full Polymorphisms in TICAM2 and IL1B are associated with TB
title_fullStr Polymorphisms in TICAM2 and IL1B are associated with TB
title_full_unstemmed Polymorphisms in TICAM2 and IL1B are associated with TB
title_short Polymorphisms in TICAM2 and IL1B are associated with TB
title_sort polymorphisms in ticam2 and il1b are associated with tb
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352113/
https://www.ncbi.nlm.nih.gov/pubmed/25521228
http://dx.doi.org/10.1038/gene.2014.77
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