TLR Signaling Pathway Gene Polymorphisms, Gene-Gene and Gene-Environment Interactions in Allergic Rhinitis.
TLR Signaling Pathway Gene Polymorphisms, Gene-Gene and Gene-Environment Interactions in Allergic Rhinitis.
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DOI：
10.2147/jir.s364877
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发表时间：
2022
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
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变应性鼻炎(AR)是一种由遗传因素和环境因素复杂相互作用引起的鼻炎性疾病。Toll样受体(Toll-like Receptor，TLR)信号通路与环境因素在AR发病机制中的关系尚不清楚。本研究旨在评估AR与TLR信号通路中单核苷酸多态(SNPs)的遗传相关性，并探讨基因-基因和基因-环境相互作用在AR中的作用。来自中国东部的452名AR患者和495名健康对照参加了以医院为基础的病例对照研究。我们评估了TLR2、TLR4和CD14基因的功能性遗传多态与AR易感性和相关临床表型的关系。用Logistic回归分析环境因素(如交通污染、居住、宠物饲养)与AR的交互作用。模型按基因和交互作用术语进行分层，并测试基因-基因和基因-环境交互作用的重要性。在单基因座分析中，CD14中的两个SNP rs2563298(A/C)和rs2569191(C/T)与AR的风险显著降低相关。与GG基因型相比，TLR2 rs7656411(G/T)的GT和GT/TT基因型与AR的危险性显著增加。基因间相互作用(如TLR2 rs7656411、TLR4 rs1927914和CD14 rs2563298)与AR相关。在AR病例中发现了基因-环境交互作用(如TLR4或CD14多态和某些环境暴露)，但经Bonferroni校正后这些交互作用并不显著。TLR2和CD14基因多态性及TLR信号通路中的基因-基因交互作用与中国汉族人群AR易感性相关。然而，目前的结果仅限于支持基因-环境交互作用与AR之间的联系。
Allergic rhinitis (AR) is a nasal inflammatory disease resulting from a complex interplay between genetic and environmental factors. The association between Toll-like receptor (TLR) signaling pathway and environmental factors in AR pathogenesis remains to be explored. This study aims to assess the genetic association of AR with single nucleotide polymorphisms (SNPs) in TLR signaling pathway, and investigate the roles of gene–gene and gene–environment interactions in AR. A total of 452 AR patients and 495 healthy controls from eastern China were enrolled in this hospital-based case–control study. We evaluated putatively functional genetic polymorphisms in TLR2, TLR4 and CD14 genes for their association with susceptibility to AR and related clinical phenotypes. Interactions between environmental factors (such as traffic pollution, residence, pet keeping) and polymorphisms with AR were examined using logistic regression. Models were stratified by genotype and interaction terms, and tested for the significance of gene–gene and gene–environment interactions. In the single-locus analysis, two SNPs in CD14, rs2563298 (A/C) and rs2569191 (C/T) were associated with a significantly decreased risk of AR. Compared with the GG genotype, the GT and GT/TT genotypes of TLR2 rs7656411 (G/T) were associated with a significantly increased risk of AR. Gene–gene interactions (eg, TLR2 rs7656411, TLR4 rs1927914, and CD14 rs2563298) was associated with AR. Gene–environment interactions (eg, TLR4 or CD14 polymorphisms and certain environmental exposures) were found in AR cases, but they were not significant after Bonferroni correction. The genetic polymorphisms of TLR2 and CD14 and gene–gene interactions in TLR signaling pathway were associated with susceptibility to AR in this Han Chinese population. However, the present results were limited to support the association between gene–environment interactions and AR.