Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent Series
BackgroundThe toll-like receptor 2 (TLR2)-mediated immune response is critical for host defense against Mycobacterium tuberculosis. There is evidence that TLR10, a TLR2 signaling modulator, may be involved in progression of tuberculosis (TB).MethodsUsing a self-validating case–control design, we tes...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-02-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00309/full |
| _version_ | 1818957476625645568 |
|---|---|
| author | Yu Wang Miao-Miao Zhang Wei-Wei Huang Shou-Quan Wu Ming-Gui Wang Xiao-Yan Tang Andrew J. Sandford Jian-Qing He |
| author_facet | Yu Wang Miao-Miao Zhang Wei-Wei Huang Shou-Quan Wu Ming-Gui Wang Xiao-Yan Tang Andrew J. Sandford Jian-Qing He |
| author_sort | Yu Wang |
| collection | DOAJ |
| description | BackgroundThe toll-like receptor 2 (TLR2)-mediated immune response is critical for host defense against Mycobacterium tuberculosis. There is evidence that TLR10, a TLR2 signaling modulator, may be involved in progression of tuberculosis (TB).MethodsUsing a self-validating case–control design, we tested for an association between seven TLR10 polymorphisms and susceptibility to TB in three independent series with two distinct populations. Single-nucleotide polymorphism (SNP) genotypes were determined by the SNPscanTM method. Three genetic models (additive, dominant, and recessive) as well as multiple-SNP score analyses were used to evaluate the risk of TB associated with the TLR10 SNPs.ResultsBy comparing TB patients with healthy controls, we observed two SNPs (rs11466617 and rs4129009) that were associated with decreased risk of TB in the Tibetan population, but did not in the Chinese Han population. Further analysis demonstrated that the rs11466617 Chengdu cohort genotype served as a protective factor against the progression of latent TB infection (LTBI) to active TB under the recessive model. None of the SNPs were significantly different in comparisons of TB-uninfected people with LTBI individuals. Additionally, when the underlying four TB-associated loci were considered together in a multiple-SNP score analysis, we observed an allele dose-dependent decrease in TB risk in Tibetans.ConclusionVariants of TLR10 may show an ethnic specificity on susceptibility to TB in Tibetan individuals. rs11466617 affected the susceptibility to progress from LTBI to active TB disease, but was not associated with the establishment of LTBI after M. tuberculosis exposure. More studies are needed to verify this genetic epidemiological result and unravel the role of TLR10 SNPs in the pathogenesis of TB. |
| first_indexed | 2024-12-20T11:10:28Z |
| format | Article |
| id | doaj.art-84e984e8995a4cb5b6fcec65cec58a76 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T11:10:28Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-84e984e8995a4cb5b6fcec65cec58a762022-12-21T19:42:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-02-01910.3389/fimmu.2018.00309319617Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent SeriesYu Wang0Miao-Miao Zhang1Wei-Wei Huang2Shou-Quan Wu3Ming-Gui Wang4Xiao-Yan Tang5Andrew J. Sandford6Jian-Qing He7Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaCentre for Heart Lung Innovation, University of British Columbia and St. Paul’s Hospital, Vancouver, BC, CanadaDepartment of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaBackgroundThe toll-like receptor 2 (TLR2)-mediated immune response is critical for host defense against Mycobacterium tuberculosis. There is evidence that TLR10, a TLR2 signaling modulator, may be involved in progression of tuberculosis (TB).MethodsUsing a self-validating case–control design, we tested for an association between seven TLR10 polymorphisms and susceptibility to TB in three independent series with two distinct populations. Single-nucleotide polymorphism (SNP) genotypes were determined by the SNPscanTM method. Three genetic models (additive, dominant, and recessive) as well as multiple-SNP score analyses were used to evaluate the risk of TB associated with the TLR10 SNPs.ResultsBy comparing TB patients with healthy controls, we observed two SNPs (rs11466617 and rs4129009) that were associated with decreased risk of TB in the Tibetan population, but did not in the Chinese Han population. Further analysis demonstrated that the rs11466617 Chengdu cohort genotype served as a protective factor against the progression of latent TB infection (LTBI) to active TB under the recessive model. None of the SNPs were significantly different in comparisons of TB-uninfected people with LTBI individuals. Additionally, when the underlying four TB-associated loci were considered together in a multiple-SNP score analysis, we observed an allele dose-dependent decrease in TB risk in Tibetans.ConclusionVariants of TLR10 may show an ethnic specificity on susceptibility to TB in Tibetan individuals. rs11466617 affected the susceptibility to progress from LTBI to active TB disease, but was not associated with the establishment of LTBI after M. tuberculosis exposure. More studies are needed to verify this genetic epidemiological result and unravel the role of TLR10 SNPs in the pathogenesis of TB.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00309/fullTLR10tuberculosislatent tuberculosis infectionpolymorphismssusceptibility |
| spellingShingle | Yu Wang Miao-Miao Zhang Wei-Wei Huang Shou-Quan Wu Ming-Gui Wang Xiao-Yan Tang Andrew J. Sandford Jian-Qing He Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent Series Frontiers in Immunology TLR10 tuberculosis latent tuberculosis infection polymorphisms susceptibility |
| title | Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent Series |
| title_full | Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent Series |
| title_fullStr | Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent Series |
| title_full_unstemmed | Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent Series |
| title_short | Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent Series |
| title_sort | polymorphisms in toll like receptor 10 and tuberculosis susceptibility evidence from three independent series |
| topic | TLR10 tuberculosis latent tuberculosis infection polymorphisms susceptibility |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00309/full |
| work_keys_str_mv | AT yuwang polymorphismsintolllikereceptor10andtuberculosissusceptibilityevidencefromthreeindependentseries AT miaomiaozhang polymorphismsintolllikereceptor10andtuberculosissusceptibilityevidencefromthreeindependentseries AT weiweihuang polymorphismsintolllikereceptor10andtuberculosissusceptibilityevidencefromthreeindependentseries AT shouquanwu polymorphismsintolllikereceptor10andtuberculosissusceptibilityevidencefromthreeindependentseries AT mingguiwang polymorphismsintolllikereceptor10andtuberculosissusceptibilityevidencefromthreeindependentseries AT xiaoyantang polymorphismsintolllikereceptor10andtuberculosissusceptibilityevidencefromthreeindependentseries AT andrewjsandford polymorphismsintolllikereceptor10andtuberculosissusceptibilityevidencefromthreeindependentseries AT jianqinghe polymorphismsintolllikereceptor10andtuberculosissusceptibilityevidencefromthreeindependentseries |