TLR Signaling Pathway Gene Polymorphisms, Gene–Gene and Gene–Environment Interactions in Allergic Rhinitis

Abstract

Ruo-Xi Chen,1,* Meng-Di Dai,1,* Qing-Zhao Zhang,1 Mei-Ping Lu,1 Mei-Lin Wang,2,3 Min Yin,1,4 Xin-Jie Zhu,1 Zhong-Fei Wu,1 Zheng-Dong Zhang,2,3 Lei Cheng1,4 1Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 4International Centre for Allergy Research, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Cheng, Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email [email protected] Zheng-Dong Zhang, Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People’s Republic of China, Email [email protected]: Background: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: allergic rhinitis, toll-like receptors, CD14, single nucleotide polymorphism, gene–gene interaction, gene–environment interaction

Keywords

• allergic rhinitis
• toll-like receptors
• cd14
• single nucleotide polymorphism
• gene-gene interaction
• gene-environment interaction.