摘要
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χ^2检验,R×C表资料的χ^2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(χ^2=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(χ^2=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(χ^2=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(χ^2=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(χ^2=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。
objective To detect and analyze the mutations of cytochrome P4502 C19(CYP2 C19) 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 CYP2 C19 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 CYP2 C19 and ABCB1 was compared by χ^2 test and χ^2 test with R×C table. Results The allelic frequencies of CYP2 C19* 2(G681 A), * 3(G636 A), *17(C806 T), and ABCB1(C3435 T) were 57.1 %, 10.0%, 1.5% and 60.1%, respectively.The frequency distribution of CYP2 C19* 1/* 1, CYP2 C19* 1/* 2, CYP2 C19* 1/* 3, CYP2 C19* 1/* 17, CYP2 C19* 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 CYP2 C19 genotype and metabolisms of clopidogrel was statistically significant among different genders (χ^2=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 (χ^2=11.408, P>0.05), and there was no statistically significant difference in metabolisms of clopidogrel among women of different age groups (χ^2=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 (χ^2=139.445, P<0.05).Conclusion CYP2 C19 * 1/* 2(42.1%) was the main genotype of cardiovascular and cerebrovascular patient
作者
蒋燕成
陈辉华
陈雅斌
陈紫萱
张志珊
JIANG Yan-cheng;CHEN Hui-hua;CHEN Ya-bin;CHEN Zi-xuan;ZHANG Zhi-shan(Department of Laboratorial Medicine,the First Hospital of Quanzhou Affiliated to Fujian Medical University,Fujian Quanzhou 362000,China)
出处
《现代检验医学杂志》
CAS
2019年第6期10-15,共6页
Journal of Modern Laboratory Medicine
