NOD2/CARD15基因突变与中国人克罗恩病相关性的研究

Study on Mutation of NOD2/CARD15 Gene in Chinese Patients with Crohn's Disease

背景:近年多项研究证明NOD2/CARD15基因序列的单核苷酸多态性(SNP)与西方白种人克罗恩病(CD)明显相关,其中3个SNP(R702W、G908R和3020insC)与CD的相关性尤为显著。目的:探讨NOD2/CARD15基因SNP与中国人CD发病的相关性及其与CD临床特点的关系。方法:选取临床资料完整的CD患者48例、溃疡性结肠炎(UC)患者和健康对照者各50例,提取人血白细胞基因组DNA,经聚合酶链反应(PCR)扩增NOD2基因全部12对外显子,纯化后直接测序,根据结果分析其突变与CD病变特点的关系。结果:CD组、UC组和健康对照组均未检出3个西方人常见的NOD2/CARD15基因多态性位点。CD组的P268S突变率显著高于UC组和健康对照组(P<0.05)。5例P268S突变的CD患者病变均位于回肠(P<0.01),4例发病年龄≤20岁(P<0.01),且均并发肠腔狭窄(P<0.01)。结论:中国人CD患者中存在NOD2/CARD15基因P268S突变,且与患者的发病年龄、病变部位和并发症相关,有必要对其功能作进一步探讨。

Background： Recently several studies identified that single nucleotide polymorphism （SNP） of NOD2/CARD15 gene was associated with Crohn＇s disease （CD） in Western Caucasian population, especially the three SNP R702W, G908R and 3020ins C. Aims： To explore the SNP of NOD2/CARD15 in Chinese CD patients and its relationship with clinical characteristics of CD. Methods： Blood samples were obtained from 48 patients with CD, 50 patients with ulcerative colitis （UC） and 50 healthy controls, respectively. Genomic DNA was extracted from the white blood cells of blood samples. The DNA fragments of 12 exons of NOD2 were acquired by polymerase chain reaction （PCR） amplification. Direct DNA sequencing was carried out after purification, and the relevance of gene mutation with the clinical characteristics of CD was analyzed. Results： None of the three groups had the commonly seen variants of NOD2/CARD15 presented in Western Caucasian population. The P268S mutation rate in CD group was significantly higher than that in UC and healthy control groups （P〈0.05）. The location of lesion of 5 patients with CD having P268S mutation was all in the terminal ileum （P〈0.01）, 4/5 patients were less than 20 years old （P〈0.01） and having small intestinal stricture （P〈0.01）. Conclusions： Some Chinese CD patients carry P268S mutation, which is related to age, location of lesion and the complications of disease. It is necessary to further identify the functional significance of this mutational change.