NOD2/CARD15基因突变与中国人克罗恩病相关性研究

NOD2/CARD15 gene mutation and Crohn′s disease in the Chinese population

背景NOD2/CARD15基因是人类克罗恩病(Crohn′sdisease,CD)第一个易感基因,既往研究发现P268S可能与中国人CD发病及临床特征相关。目的本研究旨在证实P268S与中国人CD发病及其临床特征的相关性。方法血样来自临床确诊的50例CD患者,60例溃疡性结肠炎(ulcerativecolitis,UC)患者及100例健康体检者(healthycontrols,HC)。提取人血白细胞基因组DNA,PCR扩增目的片段,PCR-RFLP发现突变位点,DNA测序证实突变位点。结果共有8例CD患者发现有P268S改变,而在UC患者和HC中分别发现2例和3例P268S改变,CD组明显高于UC和HC组(χ2=10.829,P=0.004),而UC组和HC组无明显差异。8例有P268S改变的CD患者临床特征包括病变多位于回肠,发病年龄轻(6例<20岁),常并发肠腔狭窄而需手术治疗,中-重度患者比例高。结论P268S可能是NOD2/CARD15基因中与中国人CD相关的SNP。P268S与CD患者发病年龄、病变部位及并发症及病情严重程度可能相关。

Background Previous studies have shown NOD2/CARD15 gene is the first susceptibility gene for Crohn＇s disease （CD）, and P268S has been identified to be possibly associated with CD in the Chinese population. Objective Our aims are to verify P268S which is associated with Chinese patients with CD and their clinical features. Methods Blood samples were obtained from 50 patients with CD, 60 patients with ulcerative colitis （UC）, and 100 healthy controls. We extracted DNA from patients＇ white blood cells. The target sequence of NOD2/CARD15 was acquired by PCR amplification, the mutation was detected by PCR-RFLP and verified by direct DNA sequencing. Results Eight CD patients, 2 UC patients and 3 healthy controls were found to have P268S variant. The difference between CD patients and the other 2 groups was statistically significance（X^2 = 10.829, P = 0.004）. The Clinical features of 8 CD patients were as follows： location of lesion of 7 patients were in the terminal ileum, 1 was in the colon（X^2 = 8.936, P = 0.011）. Six of them were younger than 20 years old（X^2 = 6.161, P = 0.013） and 6 of them had intestinal stricture which needs surgery（X^2 = 7.931, P = 0.005）. Six of them were severe, 2 were moderate（X^2 = 7.150, P = 0.028）. Three of them were males, 5 were females（X^2 = 1.296, P = 0.255）. Conclusion P268S variant in NOD2/CARD15 is possibly associated with CD in Chinese population. P268S variant is related to the age of patients, the location of lesions, intestinal stricture and the state of illness, but not to gender.