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[中国汉族和白种人群中Toll样受体基因多态性与炎症性肠病易感性]

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

作者信息

Shen Xiu-yun, Shi Rui-hua, Wang Ying, Zhang Hong-jie, Zhou Xi-qiao, Shen Fang-cheng, Li Ke-bei

机构信息

Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2010 May 25;90(20):1416-20.

Abstract

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.

摘要

目的

探讨Toll样受体基因多态性在中国汉族炎症性肠病(IBD)患者和白种人中的分布情况。

方法

采用聚合酶链反应和限制性片段长度多态性分析(PCR-RFLP)对113例IBD患者和120例年龄及性别匹配的健康对照者的Toll样受体2(TLR2)基因Arg677Trp和Arg753Glu、TLR4基因Asp299Gly和Thr399Ile以及TLR9基因1237T/C多态性进行基因分型。进行荟萃分析以检验TLR4 Asp299Gly和Thr399Ile多态性是否与溃疡性结肠炎(UC)或克罗恩病(CD)易感性相关,以及299Gly携带情况是否与白种人群中CD患者的表型相关。

结果

我们分别在UC患者中发现2例TLR9 1237C携带者,CD患者中发现1例,健康对照者中发现1例(CD:P = 0.361;UC:P = 0.569)。等位基因频率和基因型频率均无统计学显著差异。在IBD患者和健康对照者中均未发现TLR2基因Arg677Trp和Arg753Glu、TLR4基因Asp299Gly和Thr399Ile的突变基因型。TLR4 299G等位基因在白种人群中与CD和UC显著相关(OR = 1.29,95%CI:1.08 - 1.54,P = 0.004;OR = 1.28,95%CI:1.08 - 1.51,P = 0.004)。在T399I多态性与IBD易感性之间也检测到类似关联(OR = 1.37,95%CI:1.12 - 1.68,P = 0.002;OR = 1.46,95%CI:1.13 - 1.88,P = 0.003)。然而,未发现CD表型与299Gly携带情况之间存在显著关联。

结论

TLR2基因Arg677Trp和Arg753Glu、TLR4基因Asp299Gly和Thr399Ile以及TLR9基因1237T/C多态性与中国汉族IBD患者无关。在白种人中,TLR4 299G和399I均显著增加患CD和UC的风险。不同种族间遗传决定因素的作用可能存在显著差异。

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