中国福建泉州地区心脑血管患者 CYP2C19，ABCB1基因多态性的检测分析

目的　检测分析泉州地区心脑血管病患者氯吡格雷相关基因细胞色素 P4502C19（ CYP2C19）和三磷酸腺苷黏合 转运体B1 （ ABCB1）的突变情况。方法　收集2018 年5 月~2019 年5 月到泉州第一医院住院接受治疗的2 029 例心脑 血管病患者的全血标本，采用sanger 测序法检测 CYP2C19，ABCB1基因型，应用Hardy-Weinberg 遗传平衡吻合度检验方法， 判断选取的标本是否具有群体代表性。根据性别、年龄因素对患者进行分组，采用四格表资料的χ2 检验，R×C 表资料的 χ2 检验比较各组间氯吡格雷代谢相关基因CYP2C19，ABCB1，氯吡格雷代谢型的分布差异。结果　CYP2C19* 2（G681A）， * 3（G636A），* 17（C806T），ABCB1（C3435T）的等位基因频率分别为 57.1 %，10.0%，1.5% 和60.1%，每个等 位基因分布的观察值和预期值差异有统计学意义（χ2=0.000~3.316，均P >0.05），符合遗传平衡定律, 具有群体代表性。 CYP2C19 * 1 /* 1，CYP2C19 * 1 / * 2，CYP2C19* 1 /* 3，CYP2C19* 1 /* 17，CYP2C19* 2 /* 2，CYP2C19* 2 /* 3， CYP2C19* 2 /* 17，CYP2C19 * 3 /* 17 基因型频率分布分别为 35.5%，42.1%，6.4%，0.9%，11.1%，3.4%，0.4 % 和0.2%， 氯吡格雷超代谢型、快代谢型、中代谢型、慢代谢型的频率分别为0.9%，35.5%，49.1% 和14.5%。CYP2C19 基因型及 氯吡格雷代谢类型在不同性别之间分布差异有统计学意义（χ2=838.9~1361.134，均P <0.05），氯吡格雷代谢类型在男 性不同年龄段的差异无统计学意义（χ2=11.408，P >0.05），氯吡格雷代谢类型在女性不同年龄段的差异无统计学意义 （χ2=21.262， P >0.05）。ABCB1（C3435T）基因型CC，CT 和TT 的频率分别为39.9%，44.4% 和15.7%，ABCB1 基 因型在不同性别之间分布差异有统计学意义（χ2=139.445，P <0.05）。结论　泉州地区心脑血管患者 CYP2C19 基因型 主要以CYP2C19 * 1 /* 2 （42.1%）为主，ABCB1 基因型主要以CT（44.4%）为主，氯吡格雷代谢表型以中代谢（49.1%） 为主。CYP2C19 基因型、ABCB1 基因型及氯吡格雷代谢类型在不同性别之间是有差异的。氯吡格雷代谢类型在同性不 同年龄段是没有差异的。

Detection and Analysis of CYP2C19 and ABCB1 Gene Polymorphism in Patients with Cardiovascular and Cerebrovascular Diseases in Quanzhou of Fujian,China

objective　To detect and analyze the mutations of cytochrome P4502C19（CYP2C19） and adenosine triphosphate binding transporter B1 （ABCB1） in patients with cardiovascular and cerebrovascular diseases in Quanzhou.Methods　Whole blood samples of 2 029 patients with cardiovascular and cerebrovascular diseases admitted to Quanzhou First Hospital from May 2018 to May 2019 were collected. The genotypes of CYP2C19 and ABCB1 were detected by sanger sequencing method, and the Hardy-Weinberg genetic balance anastomosis test method was applied to determine whether the selected samples were representative of the population.The patients were divided into four groups according to gender and age, and the distribution of clopidogrel metabolization-related genes CYP2C19 and ABCB1 was compared by χ2 test and χ2 test with R×C table. Results　 The allelic frequencies of CYP2C19* 2 （G681A）, * 3（G636A）, *17（C806T）, and ABCB1（C3435T） were 57.1 %, 10.0%, 1.5% and 60.1%, respectively.The frequency distribution of CYP2C19* 1 /* 1, CYP2C19* 1 /* 2, CYP2C19* 1 /*3, CYP2C19* 1 /* 17, CYP2C19* 1 /* 17 was 35.5%, 42.1%, 6.4%, 0.9%, 11.1%, 3.4%, 0.4% and 0.2%, respectively. The frequency of hypermetabolism, fast metabolism, medium metabolism and slow metabolism were 0.9%, 35.5%, 49.1% and 14.5% respectively.The distribution of CYP2C19 genotype and metabolisms of clopidogrel was statistically significant among different genders （χ2=838.9~1 361.134, all P <0.05）, and there was no statistically significant difference in metabolisms of clopidogrel among men of different age groups （χ2=11.408, P >0.05）, and there was no statistically significant difference in metabolisms of clopidogrel among women of different age groups （χ2 =21.262, P >0.05）.The frequency of ABCB1 genotype CC, CT and TT was 39.9%, 44.4% and 15.7%, respectively. The distribution of ABCB1 genotype among different genders was statistically significant （χ2=139.445, P <0.05）.Conclusion　CYP2C19 * 1 /* 2 （42.1%） was the main genotype of cardiovascular and cerebrovascular patients in quanzhou region, while the main genotype of ABCB1 was CT（44.4%）, and the main metabolic phenotype of clopidogrel was moderate metabolism （49.1%）.The genotypes of CYP2C19, ABCB1 and clopidogrel are different between different genders.There was no difference in the metabolic pattern of clopidogrel in different age groups.