死亡受体DR4和DR5基因多态性与克罗恩病的相关性  

Associations of Crohn＇s disease with DR4 and DR5 gene polymorphisms

作　　者：林心心 金玲湘[2] 潘陈为[2] 郑淑姿 章达冠 林秀清[3] 丁然 姜利佳 蒋益[1] 

机构地区：[1]温州医科大学附属第二医院消化内科,浙江省温州市325000 [2]温州医科大学附属第二医院感染科,浙江省温州市325000 [3]温州医科大学附属第二医院附属第一医院消化内科,浙江省温州市325000 [4]温州市人民医院消化内科 [5]温州市中心医院消化内科

出　　处：《中华医学遗传学杂志》2015年第5期715-722,共8页Chinese Journal of Medical Genetics

基　　金：浙江省自然科学基金（LY14H030012）;浙江省卫生厅资助项目（2014KYB157;2012KYA132）;温州市科技局资助项目（Y20130052）

摘　　要：目的探讨死亡受体（deathreceptor，DR）4和DR5基因多态性与克罗恩病（Crohn’Sdisease，CD）的相关性。方法收集295例CD患者和490名对照者，采用SNaPshot技术检测DR4（rsl3278062和rs20575）及DR5（rsl047266）3种单核苷酸多态性（singlenucleotidepolymorphism，SNP）。经非条件Logistic回归分析各SNP的突变等位基因和基因型频率在CD组与对照组之间的差异，以及对CD患者临床病理特征的影响。采用Haploview4．2和R语言软件包进行连锁不平衡及单倍型分析。构建基因-基因交互模型，分析上述3个SNP是否对CD具有协同影响。结果CD组中DR4（rsl3278062）的突变等位基因（T）和基因型（GT＋TT）频率均高于对照组（37．12％7JS．32．04％，P=0．040，95％CI：1．010～1．550；62．71％VS．54．90％，P=0．032，95％CI：11028～1．855），而DR4（rs20575）和DR5（rsl047266）的突变等位基因和基因型频率在两组之间比较差异均无统计学意义（均P〉O．05）。CD患者按“蒙特利尔分型标准”分层，经两两比较校正检验水准后（P〈0．0125），与回结肠型CD相比较，结肠型和回肠末段型CD中DR4（rs13278062）的突变等位基因（T）和基因型（GT＋TT）频率均显著偏高[（结肠型／回结肠型：41．04％VS．25．64％，P=0．002，95％CI：0．315～0．778；66．04％735．41．03％，P=0．001，95％CI：0．196～0．655）；（回肠末段型／回结肠型：41．44％VS．25．64％，P=0．002，95％CI：0．311～0．762；74．77％WS．41．03％，P〈0．001，95％CI：0．126~0．437）]。与穿透型CD相比，狭窄型CD中DR4（rsl3278062）的突变等位基因（T）和突变基因型（GT＋TT）频率均显著降低（32．29％VS．48．91％，P=0．007，95％CI：0．3000．828；57．29％725．86．96％，P=0．001，95％CI：0．078~0．520）；非狭窄非穿透型CD中DR4（rs13278062）的突变基因型（GT＋TT）频率亦显著降低（58�Objective To assess the associations of death receptor DR4 and DR5 gene polymorphisms with Crohn＇s disease （CD）. Methods A total of 295 CD patients and 490 healthy controls were recruited. Three single nucleotide polymorphisms （SNPs） of the DR4 （rs13278062, rs20575） and DR5 （rs1047266） genes were determined with a SNaPshot method. Unconditional logistic regression analysis was carried out for determining the allelic and genotypic differences of the three SNPs between CD patients and the controls, as well as the influence of the DR4 and DR5 gene polymorphisms on the clinical features of CD patients. Linkage disequilibrium and haplotype analysis were calculated by haplotype 4.2 and R language software. A gene-gene interaction model was established to analyze whether the three SNPs can exert a synergistic effect on the susceptibility to CD. Results The mutant allele （T） and genotype （GT-k-TT） of DR4 （rs13278062） were increased among CD patients compared to the controls （37. 12% vs. 32.04%, P= 0. 040, 95%CI： 1.010-1.550; 62. 71% vs. 54. 90%, P= 0.032, 95%CI： 1. 028-1. 855, respectively）. However, the allelic and genotypic frequencies of DR4 （rs20575） and DR5 （rs1047266） did not differ between the two groups （all P〉0.05）. Based on the Montreal Classification Standards, the CD patients were stratified by locations and behaviors of the disease. After multiple comparison correction （P〈0. 0125）, compared to ileocolonic CD patients respectively, the mutant allele （T） and genotype （GT＋TT） of the rs13278062 polymorphism were significantly increased in colonic CD patients （41.04% vs. 25.64%, P= 0. 002, 95% CI= 0.315-0.778; 66.04% vs. 41.03%, P=0.001, 95%CI~ O. 196-0.655, respectively） and terminal ileum CD patients （41.44% vs. 25.64%, P= 0. 002, 95%CI： 0. 311-0. 762; 74.77% vs. 41.03M, P%0. 001, 95 %CI： 0. 126-0. 437, respectively）. In comparison to penetrating CD patients, the mutant allele （T） and genotype （GT ＋ TT） of DR4 （rs1327806

关 键 词：克罗恩病 死亡受体 TNF相关凋亡诱导配体 基因多态性 

分 类 号：R541.4[医药卫生—心血管疾病]