Synergistic effect of genetic polymorphisms in TLR6 and TLR10 genes on the risk of pulmonary tuberculosis in a Moldavian population.

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Innate Immunity Pub Date : 2021-07-01 Epub Date: 2021-07-18 DOI:10.1177/17534259211029996

Alexander Varzari, Igor V Deyneko, Elena Tudor, Harald Grallert, Thomas Illig

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引用次数: 4

Abstract

Polymorphisms in genes that control immune function and regulation may influence susceptibility to pulmonary tuberculosis (TB). In this study, 14 polymorphisms in 12 key genes involved in the immune response (VDR, MR1, TLR1, TLR2, TLR10, SLC11A1, IL1B, IL10, IFNG, TNF, IRAK1, and FOXP3) were tested for their association with pulmonary TB in 271 patients with TB and 251 community-matched controls from the Republic of Moldova. In addition, gene-gene interactions involved in TB susceptibility were analyzed for a total of 43 genetic loci. Single nucleotide polymorphism (SNP) analysis revealed a nominal association between TNF rs1800629 and pulmonary TB (Fisher exact test P = 0.01843). In the pairwise interaction analysis, the combination of the genotypes TLR6 rs5743810 GA and TLR10 rs11096957 GT was significantly associated with an increased genetic risk of pulmonary TB (OR = 2.48, 95% CI = 1.62-3.85; Fisher exact test P value = 1.5 × 10^-5, significant after Bonferroni correction). In conclusion, the TLR6 rs5743810 and TLR10 rs11096957 two-locus interaction confers a significantly higher risk for pulmonary TB; due to its high frequency in the population, this SNP combination may serve as a novel biomarker for predicting TB susceptibility.

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TLR6和TLR10基因遗传多态性对摩尔多瓦人群肺结核风险的协同作用

控制免疫功能和调节的基因多态性可能影响对肺结核(TB)的易感性。在这项研究中，我们检测了摩尔多瓦共和国271例结核病患者和251例社区匹配对照者中12个参与免疫反应的关键基因(VDR、MR1、TLR1、TLR2、TLR10、SLC11A1、IL1B、IL10、IFNG、TNF、IRAK1和FOXP3)的14个多态性与肺结核的相关性。此外，我们还分析了43个基因位点与结核易感性相关的基因-基因相互作用。单核苷酸多态性(SNP)分析显示TNF rs1800629与肺结核之间存在名义关联(Fisher精确检验P = 0.01843)。在两两相互作用分析中，TLR6 rss5743810 GA和TLR10 rs11096957 GT基因型组合与肺结核遗传风险增加显著相关(OR = 2.48, 95% CI = 1.62-3.85;Fisher精确检验P值= 1.5 × 10-5，经Bonferroni校正后显著)。综上所述，TLR6 rss5743810和TLR10 rs11096957两位点互作可显著增加肺结核的发病风险;由于其在人群中的高频率，该SNP组合可能作为预测结核病易感性的新生物标志物。

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来源期刊

Innate Immunity 生物-免疫学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Innate Immunity is a highly ranked, peer-reviewed scholarly journal and is the official journal of the International Endotoxin & Innate Immunity Society (IEIIS). The journal welcomes manuscripts from researchers actively working on all aspects of innate immunity including biologically active bacterial, viral, fungal, parasitic, and plant components, as well as relevant cells, their receptors, signaling pathways, and induced mediators. The aim of the Journal is to provide a single, interdisciplinary forum for the dissemination of new information on innate immunity in humans, animals, and plants to researchers. The Journal creates a vehicle for the publication of articles encompassing all areas of research, basic, applied, and clinical. The subject areas of interest include, but are not limited to, research in biochemistry, biophysics, cell biology, chemistry, clinical medicine, immunology, infectious disease, microbiology, molecular biology, and pharmacology.