Association between the Interaction of Key Genes Involved in Effector T-Cell Pathways and Susceptibility to Developallergic Rhinitis: A Population-Based Case-Control Association Study

作者：Zhang, Yuan; Li, Jingyun; Wang, Chengshuo^*; Zhang, Luo

来源：PLos One, 2015, 10(7): e0131248.

DOI：10.1371/journal.pone.0131248

• ALLERGIC RHINITIS
• ARIA 2008
• ASTHMA
• POLYMORPHISMS
• PREVALENCE
• MECHANISMS
• CYTOKINES
• GENETICS
• CHILDREN
• DISEASES

Background @@@ Evidence suggests that interaction between key genes mediating signaling and transcriptional networks involving effector T-cell responses may influence an individual's susceptibility to develop allergic rhinitis(AR). @@@ Objective @@@ The aim of this study was to determine whether specific interactions between key genes involved in effector T-cell pathways are associated with an individual's susceptibility to develop AR in Han Chinese subjects. @@@ Method @@@ A cohort of 489 patients with AR and 421 healthy controls was enrolled from the Han Chinese population in Beijing, China. AR was established by questionnaire and clinical examination, and peripheral blood was drawn from all subjects for DNA extraction. A total of 96 single nucleotide polymorphisms (SNPs) in 26 reprehensive candidate genes involved in T helper 1 (Th1), Th2, Th17, Th9 and T regulatory cell pathways were selected from the International Haplotype Mappingdatabase for Han Chinese in Beijing (CHB) population, and Illumina Golden Gate assay was conducted for SNP genotyping. The PLINK software package was used to perform statistical analyses. @@@ Results @@@ Simple SNP-phenotype association analysis using logistic regression showed SNP rs8193036 in IL17A gene, rs2569254 in IL-12 and rs1898413 in ROR alpha were significantly associated with AR. Simple SNP-phenotype association analysis with genetic models demonstrated thatrs2569254 in IL-12, rs1031508 in STAT4, and rs3741809 in IL-26 were likely to be recessive, rs8193036 in IL17A allelic, rs897200 in STAT4 genotypic, and rs1898413 in ROR alpha dominant. Epistasis analyses exhibited that 83 SNPs in 23 genes were significantly interactive; of which 59 interactions/SNP pairs demonstrated OR values higher than 2 or lower than 0.5, and 12 interactions/SNP pairs OR values higher than 4 or lower than 0.25. STAT3, ROR alpha and IL-26, involved in Th17 pathway, were the most frequently interactive genes. @@@ Conclusion @@@ This study suggests that interactions between several SNPs in key genes involved in effector T-cell pathways are likely to influence an individual's susceptibility to develop AR.

• 出版日期2015-7-21
• 单位首都医科大学; 北京市耳鼻咽喉科研究所