IL-6基因启动子区-174C/G、-572C/G 位点单核苷酸多态性与大动脉炎易感性之间的联系

Association of Polymorphisms of-174C/G and-572C/G in the IL-6 Promoter Region with Susceptibility to Takayasu Arteritis

目的大动脉炎(takayasu arteritis,TA)是一种主要累及大动脉及其一级分支的慢性炎症,目前TA的发病机制尚不明确,认为其发生发展与多种因素相关。白细胞介素6(interleukin 6,IL-6)与多种炎症性及免疫性疾病相关,既往研究提示IL-6启动区基因多态性可能与TA易感性相关,本研究将探讨IL-6基因启动子区-174C/G和-572C/G多态性与TA易感性之间的关联。方法纳入2011年12月~2014年1月在阜外医院确诊的111例大动脉炎患者(TA组),并选取197名健康的汉族人作为对照(对照组),描述并比较两组患者-174C/G(rs1800795)和-572C/G(rs1800796)位点的等位基因频率和基因型分布情况。结果IL-6基因启动子区-174C/G位点基因型分别CC型和CG型,-572C/G位点检测到CC、CG和GG三种基因型,且-174C/G和-572C/G等位基因和基因型频率符合哈迪-温伯格遗传平衡。IL-6-174C/G位点CC基因型的分布频率在患者组和对照组中分别为97.3%,98.5%,CG基因型分布频率分别为2.7%,1.5%;IL-6-572C/G位点CC、CG、GG基因型在患者组的分布频率分别为44.2%,48.6%,7.2%,对照组分别为45.2%、47.7%、7.1%;两个位点基因型在TA组和对照组间分布差异无统计学意义(P值分别为0.47,0.86,0.94)。-174C/G位点CC基因型与CG基因型比值比分别为1.00和0.55,P=0.47;-572C/G位点CC、CG、GG基因型比值比分别为1.00,1.04和1.03。在显性遗传模式下,-572C/G位点CC与CG+GG基因型的比值比分别为1.00和0.96;隐性遗传模式下,-572C/G位点CC+CG与GG基因型的比值比分别为1.00和1.03;共显性遗传模式下,-572C/G位点CC、CG与GG基因型的比值比分别为1.00,1.04和1.03,三种遗传模型下基因型分布在两组之间无明显差异。-174C/G和-572C/G形成的单倍型在两组研究对象中分布差异无统计学意义(P=0.83)。结论TA患者中IL-6基因启动子区-174C/G和-572C/G位点等位基因频率、基因型分布和基因型组合分布与正常人无差异,因此汉族人群中-174C/G和-572C/G基因单核酸多态性与大动脉炎易感性无关。

Objective Takayasu arteritis(TA)is a chronic inflammation mainly involved the aorta and its primary branch.The pathogenesis of TA is still unclear,and many factors influence its development.Interleukin 6(IL-6)is associated with some inflammatory and immune disease.Previous study suggested that IL-6 promoter region gene polymorphism may be associated with TA susceptibility.This study is to investigate the relationship between interleukin 6(IL-6)gene promoter region-174C/G,572C/G polymorphism and TA.Methods A total of 111 TA patients(treatment group)were enrolled in Fuwai hospital form 2011 December to 2014 January,and 197 unrelated healthy subjects(control group)were recruited.The distribution of-174C/G and-572C/G allele and genotypes of the two groups were analyzed.Results The promoter regions of IL-6-174C/G locus genotypes were CC type and CG type.The promoter regions of IL-6-572C/G were detected in CC type,GC type and GG type.IL-6-174C/G and-572C/G allele and genotype frequencies were conformed with Hardy-Weinberg equilibrium.The distribution frequency of CC genotype in IL-6-164C/G locus was 97.3%in TA group and 98.5%in control group.The frequency of CG genotype was 2.7%and 1.5%,respectively.The frequencies of CC,CG,and GG phenotypes of IL-6-572 locus were 44.2%,48.6%,and 7.2%in TA patients.Correspondingly,the frequencies of control group were 45.2%,47.7%and7.2%,respectively.There was no significant difference in the genotype distribution between the TA group and control group(P=0.47,P=0.86,P=0.94).The odds ratios(OR)of IL-6-174C/G gene CC type and CG type were 1.00 and 0.55 respectively(P=0.47).The OR of IL-6-572C/G gene CC type,CG type and GG type were 1.00,1.04 and 1.03 respectively.In dominant model,the OR of IL-6-572C/G gene CC type and CG+GG type were 1.00 and 0.96.In recessive model,the OR of IL-6-572C/G gene CC+CG type and GG type were 1.00 and 1.03.In co-dominant model,the OR of IL-6-572C/G gene CC type,CG type and GG type were 1.00,1.04 and 1.03.There were no differences in IL-6-572C/G genotype distribution under three models and in distribution of haplotypes between-174C/G and-572C/G in the two groups.Conclusion No statistical significance was observed between the TA patients and control subjects in allele distribution,allele frequencies,and combined distribution of genotypes for both-174C/G,572C/G polymorphism.The current study suggested that the susceptibility of TA is likely to be irrelevant to IL-6 gene promoter gene-174C/G and 572C/G single nucleotide polymorphism.