北方地区汉族消化道疾病中CYP2C19基因多态性分析

Distribution of CYP2C19 genetic polymorphisms in a north Chinese Han population with digestive tract diseases

目的探讨中国北方地区汉族消化道疾病患者中CYP2C19基因多态性的频率分布及其与消化道疾病的相关性。方法采用数字荧光分子探针杂交法测定1 429例北方汉族消化道疾病的CYP2C19基因型,并根据其药物代谢活性分为超快代谢(ultra-rapid metabolizer,UM)型、快代谢(extensive metabolizer,EM)型、中间代谢(intermediate metabolizer,IM)型和慢代谢(poor metabolizer,PM)型四种。结果 CYP2C19等位基因*1、*2、*3和*17的频率分别为64.3%、29.7%、4.9%和1.0%。CYP2C19 UM型患者占1.2%(17例),EM型占41.5%(593例),IM型占45.3%(647例),PM型占12.0%(172例)。幽门螺旋杆菌总体感染阳性率为75.3%,不同CYP2C19代谢型患者的感染阳性率差异无统计学意义。在非萎缩性胃炎、萎缩性胃炎、消化性溃疡、反流性食管炎、Barrett食管和胃癌等消化道疾病之间CYP2C19的代谢型分布差异无统计学意义。10例胃癌患者中有8例为IM型。结论 CYP2C19 IM型和EM型是北方地区汉族消化道疾病中常见的代谢类型,CYP2C19*2、*3及PM型的频率高于欧洲人群,而CYP2C19*17及UM型频率低于欧洲人群。

Purpose To investigate the distribution and clinical correlations of Cytochrome P450 2C19 （CYP2C19） polymorphisms in a north Chinese HaM population with digestive tract diseases. Methods CYP2C19 genotypes including ＊ 1, ＊ 2, ＊ 3 and ＊ 17 al- leles of 1 429 patients were determined using digital fluorescence molecular probe hybridization, and classified as uhra-rapid metaboli- zer （UM）, extensive metabolizer （EM）, intermediate metabolizer （IM） or poor metabolizer （PM）. Results Allele frequencies of CYP2C19 ＊ 1, ＊ 2, ＊ 3, and ＊ 17 were 64.3%, 29.7%, 4.9%, and 1.0%. Regarding CYP2C19 genotypes, 17 patients （1.2%） were classified as UM, 593 patients （41.5%） were classified as EM, 647 patients （45.3%） were classified as IM, and 172 patients （ 12. 0% ） were classified as PM. Overall H. pylori infection positive rate was 75.3%, and there was no significant differ- ence between CYP2C19 metabolic phenotype and H. pylori infection. Although there was no significant association between CYP2C19 metabolic phenotype and clinicopathologic variables, it was notable that 8 out of 10 gastric cancer patients had the IM metabolic pheno- type. Conclusion IM and EM are the most common metabolic phenotype in north Chinese HaM patients with digestive tract diseases. Compared with European poplulation, north Chinese HaM population has higher frequencies of CYP2C19 ＊ 2 and ＊ 3 alleles and poor metabolizer, but has lower frequencies of CYP2C19 ＊ 17 allele and ultra-rapid metabolizer.