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Title: [Association of Crohn's disease with aryl hydrocarbon receptor gene polymorphisms and haplotypes].
Author: Wu CQ, Cao SG, Xia XP, Xu CL, Xia SL, Lin XQ, Jin J, Ding R, Jiang Y.
Journal: Zhonghua Nei Ke Za Zhi; 2018 Jan 01; 57(1):37-43. PubMed ID: 29325309.
Abstract:
Objective: To explore the relationship of Crohn's disease (CD) susceptibility to aryl hydrocarbon receptor (AhR) polymorphisms and haplotypes in Han population in Wenzhou city, China. Methods: A total of 310 CD patients and 573 age- and sex-matched healthy controls were enrolled in our study. Three single nucleotide polymorphisms (SNPs) of AhR(rs10249788,rs2158041,rs2066853) were determined by the improved multiple ligase detection reaction technique. Unconditional logistic regression analyses was applied to analyze the allelic and genotypic differences of each SNP between CD patients and controls, as well as their influence on the clinicopathologic characteristics in CD patients. Analyses of linkage disequilibrium and haplotype were performed by Haploview 4.2 software in all study subjects. Results: Compared with the controls, the variant allele (T) and genotype (CT+TT) of (rs2158041) were evidently decreased among CD patients (19.52% vs. 25.04%, P=0.009; 34.19% vs. 44.68%, P=0.003). According to "the Montreal Classification Standards" , CD patients were divided into different subgroups. The variant allele (T) and genotype (CT+TT) of (rs2158041) were significantly lower in patients with terminal ileum CD than in controls (16.79% vs. 25.04%, P=0.005; 28.24% vs. 44.68%, P=0.001). Similar conclusions were also drawn in patients with constricting disease when compared with the controls (15.20% vs. 25.04%, P=0.003; 28.43% vs. 44.68%, P=0.003). The three SNPs above were shown to be in a linkage disequilibrium. Compared with the controls respectively, the frequency of haplotype (CCG) was increased in CD patients (44.73% vs. 39.60%, P=0.039), whereas that of haplotype (CTG) was decreased (18.02% vs. 22.78%, P=0.047). Conclusions: AhR (rs2158041) variation might influence the risk as well as the location and behavior of CD. The haplotype (CCG) possibly increase the risk of CD development, whereas haplotype (CTG) might decrease it. 目的： 探讨浙江温州地区汉族人群中芳香烃受体(AhR)基因多态性及单倍型与克罗恩病(CD)易感性的关系。 方法： 收集310例CD患者和573名年龄、性别相匹配的健康对照者。采用"改良多重高温连接酶检测反应技术"检测AhR (rs10249788、rs2158041、rs2066853)3种单核苷酸多态性(SNP)。采用非条件logistic回归分析CD组和对照组间各SNP的等位基因和基因型频率差异及其对CD患者临床病理特征的影响。采用Haploview4.2软件进行连锁不平衡和单倍型分析。 结果： CD组中rs2158041的变异等位基因T和基因型CT+TT频率显著低于对照组(19.52%比25.04%, P=0.009; 34.19%比44.68%, P=0.003)。依据"蒙特利尔CD表型分型标准"将患者分层，回肠末端型CD患者中rs2158041的变异等位基因T和基因型CT+TT频率低于对照组(16.79%比25.04%, P=0.005; 28.24%比44.68%, P=0.001)。狭窄型CD患者中rs2158041的变异等位基因T和基因型CT+TT频率亦低于对照组(15.20%比25.04%, P=0.003; 28.43%比44.68%, P=0.003)。Haploview 4.2软件分析显示上述3种SNP(rs10249788、rs2158041、rs2066853)彼此连锁，且CD组中单倍型CCG的频率高于对照组(44.73%比39.60%, P=0.039)，而CTG的频率低于对照组(18.02%比22.78%, P=0.047)。 结论： AhR基因rs2158041变异可能影响CD发病风险、疾病部位和疾病行为。AhR(rs10249788、rs2158041、rs2066853)构建的单倍型CCG可能提高CD发病风险，而单倍型CTG则可能降低CD发病风险。.

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