T细胞免疫球蛋白和黏蛋白3基因多态性与克罗恩病的关系

Association of Crohn＆#39;s disease with T cell immunoglobulin and mucin domain 3 gene polymorphisms in Chinese patients

目的 在浙江籍汉族人群中探讨T细胞免疫球蛋白和黏蛋白3（Tim-3）基因多态性与克罗恩病（CD）的关系.方法 收集308例CD患者和573例年龄、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Tim-3的2种单核苷酸多态性（SNP）位点rs1036199和rs 10515746,采用Haploview 4.2软件进行连锁不平衡及单倍型分析.结果 CD组和对照组之间整体比较,rs1036199和rs10515746的等位基因和基因型频率的差异均无统计学意义（P均＞0.05）.依据蒙特利尔CD表型分类法将患者分层,结果显示穿透型CD患者中rs1036199的变异等位基因（C）和基因型（AC＋ CC）的频率明显高于对照组（10.4％比1.7％,P=0.002;20.8％比3.5％,P=0.023）;rr10515746的变异等位基因（A）和基因型（CA＋ AA）频率亦明显高于对照组（10.4％比2.2％,P=0.000;20.8％比4.2％,P=0.033）.经Haploview 4.2软件分析发现,rs1036199和rs10515746紧密连锁（D＆#39;=1.0,r2=0.928）.穿透型CD患者与对照组相比,由rs1036199和rs10515746各自的野生等位基因（A）、（C）构建的单倍型（AC）频率更低（89.6％比98.3％,OR=0.153,95％ CI0.055～0.426,P =0.000）,而由这2个SNP各自的变异等位基因（C）、（A）构建的单倍型（CA）频率更高（10.4％比1.6％,OR=7.287,95％ CI 2.584 ～ 20.545,P=0.000）.结论 Tim-3的2种SNP（rs1036199和rs10515746）变异可能增加穿透型CD的发病风险,由这2种SNP构建的单倍型（AC）和（CA）可能分别是穿透型CD的保护因素和危险因素.

Objective To explore the association of Crohn＆#39;s disease （CD） with T cell immunoglobulin and mucin domain 3 （Tim-3） gene polymorphisms in patients of Zhejiang Han population in China.Methods A total of 308 CD patients and 573 age-and sex-matched healthy controls were enrolled in our study.Two single nucleotide polymorphisms （SNPs） of Tim-3 （rs1036199 and rs10515746） were examined by the improved multiple ligase detection reaction technique （iMLDR）.Analyses of linkage disequilibrium and haplotype were also performed by Haploview 4.2 software in all study subjects.Results In general,the allele and genotype frequencies of Tim-3 （rs1036199 and rs10515746） were not statistically different between CD patients and the controls （all P 〉0.05）.According to ＆quot;the Montreal Classification＆quot;,CD patients were divided into different subgroups.The variant allele （C） and genotype （AC ＋ CC） of rs1036199 were more frequent in CD patients with penetrating diseases than in the controls （10.4% vs 1.7%,P =0.002;20.8% vs 3.5%,P =0.023）.Similar conclusions were also drawn for the variant allele （A） and genotype （CA ＋ AA） of rs10515746 in patients with penetrating diseases when compared with the controls （10.4% vs 2.2%,P =0.000;20.8% vs 4.2%,P =0.033,respectively）.The two SNPs of Tim-3 were in strong linkage disequilibrium （D＆#39;=1.0,r2 =0.928）.The haplotype （AC） formed by their wild-type alleles （A） and （C） was decreased in patients with penetrating CD compared with the controls （89.6% vs 98.3%,P =0.000）.However,the haplotype （CA） formed by their variant alleles was more frequent in patients with penetrating CD than in the controls （10.4% vs 1.6%,P =0.000）.Conclusions Tim-3 （rs1036199 and rs10515746） variations might be correlated with the enhanced risk of penetrating diseases in CD patients.Furthermore,the haplotype （AC） and （CA） formed by the two SNPs might be a protective and a risky factor for penetrating CD respectively.