芳香烃受体基因多态性及单倍型与溃疡性结肠炎的关系  

Correlation between aryl hydrocarbon receptor gene polymorphisms and haplotypes and ulcerative colitis

作　　者：吴利敏 吴超群[1] 黄小春 骆家凯 叶子煊 洪伟军 林子健 蒋益[1] Wu Limin;Wu Chaoqun;Huang Xiaochun;Luo Jiakai;Ye Zixuan;Hong Weijun;Lin Zijian;Jiang Yi(Department of Gastroenterology,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou City,Zhejiang Province 325000,China)

机构地区：[1]温州医科大学附属第二医院消化内科,浙江省325000

出　　处：《中华消化杂志》2018年第8期548-553,共6页Chinese Journal of Digestion

基　　金：浙江省自然科学基金（LY14H030012、LY15H030018、LY16H160055、LY17H03D011）;浙江省卫生厅资助项目（2012KYA132）;温州市科技局资助项目（Y20160102、Y20170314、Y20170062）

摘　　要：目的探讨芳香烃受体（AhR）基因多态性及单倍型与UC易感性的关系。方法选取2010年1月至2017年10月温州医科大学附属第二医院和第一医院、温州市中心医院及温州市人民医院396例UC患者为UC组，同期573名性别、年龄相匹配的健康体格检查者为健康对照组。采用改良多重高温连接酶检测反应技术检测AhR（rs10249788、rs2066853、rs2158041）3个单核昔酸多态性（SNP）。采用非条件logistic回归分析各SNP的突变等位基因和基因型频率差异及其与UC临床病理特征的关系。采用Haploview4．2软件进行连锁不平衡分析。结果UC组中AhR（rsl0249788）的突变等位基因C及基因型TC＋CC频率高于健康对照组[7S．00％（594／792）比69．98％（802／1146），95．45％（378／396）比91．10％（522／573）]，OR（95％CI）分别为1．287（1．049～1．579）和2．052（1．180～3．568），差异均有统计学意义（P=0．016、0．011）。与远端结肠炎患者相比，广泛结肠炎患者中AhR（rsl0249788）的突变等位基因C及基因型TC＋CC频率增高E71．34％（341／478）比80．57％（253／314），93．31％（223／239）比98．73％（155／157）]，OR（95％CI）分别为1．666（1．183～2．347）和5．561（1．260～24．530），差异均有统计学意义（P=0．003、0．023）。连锁不平衡分析显示，rsl0249788和rs2066853、rsl0249788和rs2158041、rs2066853和rs2158041彼此连锁（D’=0．636、0．430、0．980，r^2=0．270、0．023、0．177）。与健康对照组相比，UC组中单倍型TAC的频率降低[20．20％（231．5／1146．0）比16．24％（128．6／792．O）]，CAC的频率增高[14．43％（165．4／1146．0）比20．47％（162．1／792．0）]，OR（95％CI）分别为0．767（O．605～O．973）和1．529（1．204～1．941），差异均有统计学意义（P=0．029、P〈0．01）。进一步分析发现，广泛结肠炎患者中单倍型CGC的频率高于远�Objective To investigate the correlation between aryl hydrocarbon receptor （AhR） gene polymorphisms and haplotypes and susceptibility of ulcerative colitis （UC）. Methods From January 2010 to October 2017, at the Second Affiliated Hospital of Wenzhou Medical University, the First Affiliated Hospital of Wenzhou Medical University, Central Hospital of Wenzhou City and Wenzhou People Hospital, a total of 396 UC patients were recruited as the UC group. In the same period, 573 age- and gender-matched healthy individuals were taken as the healthy control group. Three single nucleotide polymorphisms （SNP） of AhR （rs10249788, rs2066853, rs2158041） were examined by modified multiple ligase detection reaction technique. The correlation between the differences in the frequency of each SNP mutant alleles, genotypes and clinical pathological features of UC was analyzed by unconditional logistic regression analysis. Haploview 4. 2 software was applied to analyze the linkage disequilibrium （LD）. Results The frequency of mutant allele C and genotype TCq-CC of AhR （rs10249788） of UC group were higher than those of the healthy control group （75.00%, 594/792 vs. 69.98%, 802/1 146; 95.45%, 378/396 vs. 91.10%, 522/573）, the differences were statistically significant （odds ratio （OR）= 1. 287, 95% confidence interval （CI） 1. 049 to 1. 579, P=0. 016~ OR=2. 052, 95%CI 1. 180 to 3. 568, P= 0. 011）. Compared with the patients with distal colitis, the frequencies of mutant allele C and genotype TCq- CC of AhR （rs10249788） were higher in the patients with extensive colitis （71. 34%, 341/478 vs. 80.57%, 253/314% 93. 31%, 223/239 vs. 98. 73%, 155/157）, and the differences were statistically significant （OR= 1. 666, 95%CI 1. 183 to 2. 347, P=0. 003; OR= 5. 561, 95%CI 1. 260 to 24. 530, P= 0. 023）. The results of LD analysis indicated that rs10249788 and rs2066853, rs10249788 and rs2158041, rs2066853 and rs2158041 were linked to each other （D＇=0. 636, 0. 430 and 0. 980~ r2 =0. 270, 0. 023 a

关 键 词：结肠炎 溃疡性 多态现象 遗传 单元型 芳香烃受体 

分 类 号：R574.62[医药卫生—消化系统]