T细胞免疫球蛋白和黏蛋白3基因多态性与溃疡性结肠炎的关系  

Relationship between gent polymorphisms of T cell immunogiobulin domain and mucin domain protein-3 andulcerative colitis

作　　者：林道泼 薛战雄[1] 蔡振寨[1] 夏宣平[1] 曹曙光[1] 卢光荣[1] 林秀清[2] 金捷 丁然 蒋益[1] Lin Daopo Xue Zhanxiong Cai Zhenzhai Xia Xuanping Cao Shuguang Lu Guangrong Lin Xiuqing Jin Jie Ding Ran Jiang Yi(Department of Gastroenterology, The Second Affiliated Hospital and Yuying Childrenls Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, Chin)

机构地区：[1]温州医科大学附属第二医院育英儿童医院消化内科,浙江省325000 [2]温州医科大学附属第一医院消化内科 [3]温州市中心医院消化内科 [4]温州市人民医院消化内科

出　　处：《中华消化杂志》2017年第9期612-618,共7页Chinese Journal of Digestion

基　　金：浙江省自然科学基金（LY14H030012、LY15H030018、LY16H160055、LY17H030011）;浙江省卫生厅资助项目（2012KYA132）;温州市科技局资助项目（Y20150157、Y20160102）

摘　　要：目的探讨浙江籍汉族人群中T细胞免疫球蛋白和黏蛋白（Tim）-3基因多态性与UC的关系。方法收集391例UC患者和573名健康体格检查者。采用改良多重高温连接酶检测反应技术检测Tim-3（rs1036199和rs10515746）2个单核苷酸多态性（SNP）。采用卡方检验或Fisher确切概率法分析Tim-3基因多态性分布差异及其对患者疾病部位和疾病严重程度的影响，运用Haploview 4.2软件进行连锁不平衡和单倍型分析。结果UC组中rs10515746的基因型CA＋AA和突变等位基因A频率均低于健康对照组[1.79%（7/391）比4.19%（24/573），0.90%（7/782）比2.18%（25/1 146）]，差异均有统计学意义（χ2＝4.295、4.712，P＝0.038、0.030）；UC组和健康对照组rs1036199的基因型CA＋CC和突变等位基因C的频率[1.79%（7/391）比3.49%（20/573），0.90%（7/782）比1.74%（20/1 146）]比较差异均无统计学意义（P均〉0.05）。轻中度UC患者中rs10515746的基因型CA＋AA和突变等位基因A的频率均高于重度UC患者[2.87%（7/244）比0，1.43%（7/488）比0]，差异均有统计学意义（Fisher确切概率法，P＝0.048、0.049）。连锁不平衡分析显示，rs1036199和rs10515746彼此紧密连锁（D′＝0.92，r2＝0.72）。UC患者中，由这2个SNP的突变等位基因C和A构建的单倍型CA的频率低于健康对照组[0.64%（5/782）比1.74%（20/1 146）]，差异有统计学意义（χ2＝4.441，P＝0.035）。结论Tim-3 rs10515746基因突变不仅可能降低UC发病风险，还可能减轻患者疾病严重程度。由rs1036199和rs10515746的突变等位基因构建的单倍型CA也可能降低UC发病风险。ObjectiveTo investigate the relationship between gene polymorphisms of T cell immunoglobulin domain and mucin domain protein-3 （Tim-3） and ulcerative colitis （UC） in Han nationality of Zhejiang.MethodsA total of 391 UC patients and 573 healthy controls were recruited. Two single nucleotide polymorphisms （SPNs） of Tim-3 （rs1036199 and rs10515746） were examined by the improved multiple ligase detection reaction technique. Chi-square test or Fisher′s exact test was performed to analyze the differences in the distribution of Tim-3 gene polymorphisms and its influence on the location and severity. Haploview 4.2 software was used to analyze linkage disequilibrium （LD） and haplotype.ResultsThe frequencies of genotype CA＋ AA and mutant allele A of rs10515746 in UC were lower than those in healthy controls （1.79%, 7/391 vs 4.19%, 24/573; 0.90%, 7/782 vs 2.18%, 25/1 146; χ2= 4.295 and 4.712, P=0.038 and 0.030）. However, there was no significant differences in frequencies of genotype CA＋ CC and mutant allele C of gene rs1036199 between UC patients and the healthy controls （1.79%, 7/391 vs 3.49%, 20/573; 0.90%, 7/782 vs 1.74%, 20/1 146; both P〉0.05）. The frequencies of genotype CA＋ AA and mutant allele A of rs10515746 in mild and moderate UC patients were both higher than those in severe UC patients （2.87%, 7/244 vs 0; 1.43%, 7/488 vs 0）, and the differences were statistically significant （Fisher′s exact test, P=0.049 and 0.048）. The analysis for LD indicated that rs1036199and rs10515746 were close LD （D′=0.92, r2=0.72）. Furthermore, the frequency of haplotype CA formed by the mutant alleles C and A of these two SNPs was lower in UC patients than that in healthy controls （0.64%, 5/782 vs 1.74%, 20/1 146）, and the difference was statistically significant （χ2=4.441, P=0.035）.ConclusionsTim-3 （rs10515746） gene mutation may not only decrease the incidence, but also reduce the severity of UC. Moreover, the haplotype CA formed by the mutant alleles of rs1036199 an

关 键 词：T细胞免疫球蛋白和黏蛋白3 结肠炎 溃疡性 基因 多态性  单核苷酸 

分 类 号：R574.62[医药卫生—消化系统]