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Infect Genet Evol. 2018 Jul;61:53-59. doi: 10.1016/j.meegid.2018.02.021. Epub 2018 Feb 15.

Variants of TLR1 associated with tuberculosis susceptibility in the Chinese Tibetan population but not in Han Chinese.

Author information

1
Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
2
Department of Respiratory Diseases, Chengdu Municipal First People's Hospital, Chengdu 610041, Sichuan, China.
3
Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, Vancouver, BC, Canada.
4
Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: jiangqing_he@scu.edu.cn.

Abstract

Toll-like receptor 1 (TLR1) participates in the innate immune response to Mycobacterium tuberculosis. This study mainly investigated the relationship between polymorphisms of TLR1 and tuberculosis (TB) susceptibility in the two Chinese populations. Totally, 1185 Han and 1216 Tibetan participants were enrolled. TagSNPs of TLR1 were selected and genotyped. Analyses of linkage disequilibrium and haplotypes were performed by software Haploview and SHEsis. Gene-gene interactions were evaluated using the nonparametric multifactor dimensionality reduction (MDR) method. Gene-by-sex interaction in the Tibetan population and gene-by-smoking interaction in the Han population were also calculated. Association between rs4833095 and TB susceptibility was evaluated by meta-analysis. In the Tibetan population, the A alleles of rs5743557 and rs5743596 were related with reduced tuberculosis risk (p < 0.001 and p = 0.001) after adjusting for confounding factors. Additionally, rs5743604_A was associated with increased TB susceptibility (p = 0.004). The frequency of haplotype rs4833095-rs5743557-rs5743596-rs5743604 CAAG was significantly higher in the healthy controls (HC) group (p = 0.0009), while frequency of haplotype CGGA was higher in the TB group (p = 0.001). Significant associations were detected between rs4833095-rs5743557-rs5743604 interactions and TB susceptibility. Interactions between rs5743596 and sex in the Tibetan population, between rs5743604 and smoking in the Han population were revealed as well. However, no significant main effects were observed in the Han population. The rs4833095 was not associated with TB susceptibility after meta-analysis either. Our study suggested that SNPs of the TLR1 gene were associated with TB susceptibility in the Chinese Tibetan population, but not in the Han population.

KEYWORDS:

Single nucleotide polymorphisms; Toll-like receptor 1; Tuberculosis

PMID:
29454979
DOI:
10.1016/j.meegid.2018.02.021
[Indexed for MEDLINE]

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