白细胞介素-6受体基因非同义变异rs2228145和中国过敏性鼻炎病人的相关性研究

Non-synonymous variant rs2228145 in interleukin-6 receptor(IL-6R) gene is associated with allergic rhinitis in Chinese subjects

目的过敏性鼻炎是鼻部黏膜的慢性炎性疾病,其发病受遗传和环境因素双重影响,过敏性鼻炎和哮喘在临床表现和遗传基础具有交叉重叠。本研究拟对在全基因组关联分析中发现的和哮喘相关的白细胞介素-6受体(interleukin-6 receptor,IL-6R)基因的rs2228145位点进行分析,检测其和中国过敏性鼻炎病人的相关性。方法收集402例明确诊断为过敏性鼻炎病人,以及416例正常对照,所有个体均为中国汉族。从外周血白细胞提取基因组DNA,应用时间飞行质谱的方法进行基因分型。结果等位基因分析显示过敏性鼻炎及正常对照在IL-6R基因的rs2228145位点等位基因频率存在差异(P=0.0039,Pcorrected=0.001 6)。基因型分析进一步验证了该位点和过敏性鼻炎的相关性,共显性模型(PA/C vs A/A=0.000,ORA/C vs A/A=0.546,95%CI:0.389~0.766)和显性模型(PA/C+C/C vs A/A=0.001,ORA/C+C/C vs A/A=0.575,95%CI:0.418~0.790)分析在病例组和对照组差异有统计学意义。结论结果提示和哮喘相关基因IL-6R的rs2228145位点和过敏性鼻炎的发病有关,可降低其发病的风险。

Objective Allergic rhinitis（AR） is a complex chronic inflammatory disease of the nasal mucosa,caused by an interaction between genetic and environmental factors. As evidence suggests that a proportion of individuals with AR also present symptoms of asthma and some genetic variants may have increased susceptibility to both AR and asthma. The objective of this study was to identify whether asthma susceptibility variant rs2228145 in interleukin-6 receptor（IL-6R） is associated with AR in the Chinese population.Methods A cohort of 402 individuals with physician diagnosed AR and 416 healthy controls were recruited from the Han Chinese population in Beijing. DNA was extracted from the peripheral blood. rs2228145 was genotyped using the sequenom mass array technology platform. Results Analysis of frequency differences of allele between the AR patients and control subjects showed that rs2228145 in IL-6R was significantly associated with AR（P = 0. 0039,Pcorrected= 0. 001 6）. Genotype analysis further confirmed the difference in distribution of this variant between AR patients and controls in both the co-dominant（PA/C vs A/A= 0. 000,ORA/C vs A/A= 0. 546,95% CI：0. 389-0. 766） and dominant（PA/C ＋ C/C vs A/A= 0. 001,ORA/C ＋ C/C vs A/A= 0. 575,95% CI： 0. 418-0. 790） models. Conclusion These results suggest that the rs2228145 in IL-6R gene is associated with decreased risk for AR.