Toll-like receptor 1(TLR1) Gene SNP rs5743618 is associated with increased risk for tuberculosis in Han Chinese children.

Abstract

Toll-like receptor 1 (TLR1) recognizes lipopeptides with TLR2, and affects immune response to Mycobacterium tuberculosis infection. Here, we report results of the first case-control pediatric study of the TLR1 single-nucleotide polymorphisms and susceptibility to tuberculosis (TB). A pediatric case-control study enrolled 340 TB patients and 366 healthy controls, all Han Chinese from North China. Significant differences of the allelic and genotypic distributions of rs5743618 in TLR1 gene were observed between TB group and control group and, G allele of rs5743618 was associated with increased risk for TB (OR: 2.40, 95%CI: 1.41-4.07, P = 0.0009). TLR1 rs5743618 -GT genotype was related to reduction in surface expression of TLR1 in monocytes and granulocytes regardless of stimulation with inactivated H37Rv. In addition, after stimulated with inactivated lysate of M. tuberculosis strain H37Rv, samples of peripheral blood mononuclear cells (PBMCs) from children with the rs5743618 GT genotypes showed a decreased level of Tumor Necrosis Factor-a (TNF-a) and CXC chemokine ligand 10 (CXCL10) production, invariable production of interleukin-6 (IL-6) and IL-8 and increased production of IL-10 ex vivo. To conclude, TLR1 rs5743618 G allele was found associated to susceptibility to TB in Han Chinese pediatric population. TLR1 rs5743618-GT genotype carriers may have reduced immune response to MTB infection although further study is warranted to test this conclusion.

• Authors: Hui Qi, Lin Sun, Xirong Wu, Yaqiong Jin, Jing Xiao, Shengfeng Wang, Chen Shen, Ping Chu, Zhan Qi, Fang Xu, Yajie Guo, Weiwei Jiao, Jianling Tian, Adong Shen
• Journal: Tuberculosis (Edinburgh, Scotland) (Tuberculosis (Edinb)) Vol. 95 Issue 2 Pg. 197-203 (Mar 2015) ISSN: 1873-281X [Electronic] Scotland
• PMID: 25544311 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• CXCL10 protein, human
• Chemokine CXCL10
• Interleukins
• Toll-Like Receptor 1
• Tumor Necrosis Factor-alpha

Topics

• Case-Control Studies
• Cells, Cultured
• Chemokine CXCL10 (biosynthesis)
• Child
• Child, Preschool
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Granulocytes (immunology)
• Humans
• Infant
• Interleukins (biosynthesis)
• Male
• Monocytes (immunology)
• Polymorphism, Single Nucleotide
• Toll-Like Receptor 1 (genetics, metabolism)
• Tuberculosis (genetics, immunology)
• Tumor Necrosis Factor-alpha (biosynthesis)