Toll样受体基因多态性与中国江苏地区汉族人群和白种人群炎症性肠病的相关性

Toll-like receptor gene polymorphisms and susceptibility to inflammatory bowel disease in Chinese Han and Caucasian populations

目的 探讨Toll样受体基因多态性与中国人群和白种人群炎症性肠病（IBD）易感性的相关性.方法 采用聚合酶链反应.限制性片段长度多态性方法,检测113例江苏地区汉族IBD患者与120名正常对照者TLR2基因Arg677Trp、Arg753Glu,TLR4基因Asp299Gly、Thr399Ile及TLR9基因1237T/C基因型,分析这些Toll样受体基因位点的多态性与IBD发病的相关性;对白种人群中TLR4Asp299Gly、Thr399Ile两个单核苷酸多态性位点的多态性与IBD易感性及临床表型的关系进行荟萃分析.结果 在所检测的IBD患者和正常对照者中有2例溃疡性结肠炎（UC）患者、1例克罗恩病（CD）患者及1名正常对照者存在TLR91237T/C杂合突变（CD：P=0.361,UC：P=0.569）,差异无统计学意义,在IBD患者及正常人群中均未发现TLR2基因Arg677Trp、Arg753Glu,TLR4基因Asp299Gly、Thr399Ile突变型;荟萃分析发现白种人CD和UC患者TLR4基因Asp299Gly（CD：OR=1.29,95%CI：1.08～1.54,P=0.004;UC：OR=1.28,95%CI：1.08～1.51,P：0.004）、Thr399Ile（CD：OR=1.37,95%CI：1.12～1.68,P=0.002;UC：OR=1.46,95%CI：1.13～1.88,P=0.003）突变发生率均明显高于正常对照者,Asp299Gly多态性与CD临床表型无明显相关性.结论 未发现TLR2基因Arg677Trp、Arg753Glu,TLR4基因Asp299Gly、Thr399Ile及TLR9基因1237T/C多态性与江苏地区汉族人群IBD的易感性相关;荟萃分析显示,TLR4基因Asp299Gly、Thr399Ile多态性与白种人CD和UC发病相关,IBD的遗传易感性具有种族差异性.

Objective To explore the distribution of Toll-like receptors gene polymorphisms in inflammatory bowel disease （IBD） in Chinese Han patients and Caucasians. Methods The toll-like receptor 2 （TLR2） genes Arg677Trp and Arg753Glu, TLR4 genes Asp299Gly and Thr399Ile, and TLR9 gene 1237T/C polymorphisms were genotypes in 113 patients with IBD and 120 age and gender-matched healthy controls by the analyses of polymerase chain reaction and restriction fragment length polymorphism （PCR-RFLP）.A meta-analysis was performed to test whether TLR4 Asp299Gly and Thr399Ile polymorphisms were associated with ulcerative colitis （UC） or Crohn＇s disease （CD） susceptibility and whether 299Gly carriage was associated with phenotypes of CD patients in the Caucasian population. Results We found two carriers of TLR9 1237C in UC patients, one carrier in CD patients and one in healthy controls respectively（CD：P=0. 361;UC：P=0. 569） . There was no statistically significant difference in both allelic and genotypic frequencies. The mutant genotypes of TLR2 gene Arg677Trp and Arg753Glu, TLR4 gene Asp299Gly and Thr399Ile were not found in either the IBD patients or the healthy controls. The TLR4 299G allele showed a significant association with CD and UC in Caucasian population （OR=1. 29,95% CI：1. 08-1. 54,P=0. 004 and OR=1. 28, 95% CI：1. 08-1. 51, P=0. 004 respectively） . Similar association was detected between T399I polymorphism and susceptibility to IBD （OR=1.37,95% CI：1. 12-1. 68, P=0. 002 and OR=1. 46, 95% CI：1. 13-1. 88,P=0. 003 respectively）. However, no significant association was identified between CD phenotypes and 299Gly carriage. Conclusion TLR2 genes Arg677Trp and Arg753Glu,TLR4 genes Asp299Gly and Thr399Ile and TLR9 gene 1237T/C polymorphisms are not associated with IBD in Chinese Han patients.In Caucasians.both TLR4 299G and 399I confer a significant risk for developing CD and UC.The contribution of genetic determinants may differ significantly between ethnicities.