福建汉族氯吡格雷药物代谢相关基因CYP2C19的多态性分布研究

Prevalence of CYP2C19 polymorphisms involved in clopidogrel metabolism in Fujian Han population

目的探讨中国福建汉族人群与氯吡格雷代谢相关的CYP2C19基因多态性的分布。方法采用聚合酶链反应-限制性片段长度多态性检测以及直接测序对1001名无亲缘关系的福建汉族志愿者进行CYP2C19＊2、CYP2C19＊3以及CYP2C19＊17基因型的检测。结果在全部对象中，CYP2C19＊2、＊3和＊17的频率分别为32．4％、5．8％和0．4％。根据CYP2C19基因多态位点功能代谢分型，携带CYP2C19＊2或＊3的中间代谢型（＊1／＊2和＊1／＊3）与弱代谢型（＊2／＊2和＊2／＊3）分别占47．95％和13．99％。该结果与日本、韩国、新加坡、马来西亚、泰国人群及中国的傣族、蒙古族、黎族和回族相似（P〉O．05），但是与中国的哈萨克族及维吾尔族，以及伊朗、俄罗斯、意大利、波兰、挪威、加拿大印第安人、玻利维亚、埃及、坦桑尼亚等国家的人种差异有统计学意义（P〈O．05）。结论氯吡格雷药物代谢相关基因CYP2C19的分布存在种族（地区）差异。该多态在中国福建汉族人群中的分布与中国傣族、蒙古族、黎族、回族及部分东亚、东南亚人群无明显差异，但与中国哈萨克族和维吾尔族以及部分欧洲、南美洲和非洲人群相比有较多的中间代谢型及弱代谢型（P〈O．05）。

Objective To investigate the frequency of CYP2C19 polymorphisms involved in clopidogrel metabolism in Fujian Han population. Methods Frequencies of CYP2C19 ＊ 2, CYP2C19 ＊ 3 and CYP2C19 ＊ 17 in 1001 unrelated Fujian Han volunteers were determined with polymerase chain reaction- restriction fragment length polymorphism and direct sequencing method. Results The frequencies of CYP2C19 ＊ 2, ＊ 3 and ＊ 17 were 32.4%, 5.8% and 0.4%, respectively. According to genotyping results, intermediate metabolizers （CYP2C19 ＊ 1/＊ 2 or ＊ 1/＊ 3） and poor metabolizers （CYP2C19 ＊ 2/＊ 2 and ＊ 2/＊ 3） respectively accounted for 47.95% and 13.99% of all subjects. Above frequencies were similar to those of Japan, Korea, Singapore, Malaysia, Thailand and Chinese Dai, Mongolian,Li and Hui ethnics （P ~0.05）, but were significantly different from those of Chinese Kazakh and Uygur ethnics, and people from Iran, Russia, Italy, Poland, Norway, Canada native Indians, Bolivia, Egypt or Tanzania （P^0. 05）. Conclusion Ethnic/regional diversity exist with regard to the prevalence of CYP2C19 polymorphisms. No significant difference were found between Fujian Han Chinese and Dai, Mongolian, Li and Hui from China or other populations from East and Southeast Asia, but higher frequencies of intermediate metabolizers and poor metabolizers compared with populations of Kazakh and Uygur in China, and people from Europe, South America and Africa.