中国南方地区客家人群CYP2C9和VKORC1-1639G>A基因的遗传多态性  

Genetic Polymorphisms of CYP2C9 and VKORC1-1639G>A Genes in A South⁃ern Chinese Hakka Population

作　　者：丘小红 侯经远 邓巧亭 邓勋伟 钟志雄[3,4] QIU Xiaohong;HOU Jingyuan;DENG Qiaoting;DENG Xunwei;ZHONG Zhixiong(Guangdong Medical University,Zhanjiang,Guangdong 524023,China;Research and Experimental Center,Meizhou People's Hospital,Meizhou,Guangdong 514031,Chin;Cardiovas-cular Diseases Center,Meizhou People's Hospital,Meizhou,Guangdong 514031,China;Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population,Meizhou,Guangdong 514031,China)

机构地区：[1]广东医科大学,广东湛江524023 [2]梅州市人民医院科研实验中心,广东梅州514031 [3]梅州市人民医院心血管疾病中心,广东梅州514031 [4]广东省客家人群精准医学与临床转化研究重点实验室,广东梅州514031

出　　处：《岭南心血管病杂志》2023年第6期605-610,632,共7页South China Journal of Cardiovascular Diseases

基　　金：国家自然科学青年基金(项目编号:82002216);广东省客家人群精准医学与临床转化研究重点实验室(项目编号:2018B030322003);梅州市科技计划项目(项目编号:2019B0202001)。

摘　　要：目的 探讨华法林药物反应相关基因细胞色素氧化酶P4502C9(cytochrome P450 family 2 subfamily C polypeptide,CYP2C9)和维生素K环氧化物还原酶复合体亚基1(vitamin K epoxide reductase subunit 1,VKORC1)-1639G>A遗传多态性在中国南方客家人群中的分布。方法 本研究共纳入2015年7月至2019年1月来梅州市人民医院门诊及住院口服华法林抗凝治疗的患者1 330例,提取患者外周血基因组DNA,通过聚合酶链反应(polymerase chain reaction,PCR)和DNA微阵列芯片法检测CYP2C9和VKORC1-1639G>A基因多态性。将中国南方客家人群CYP2C9和VKORC1-1639G>A基因型和基因频率与文献已报道的不同地区人群和民族的频率进行比较。结果 经Hardy-Weinberg Equilibrium遗传平衡定律检验,所有基因型均符合遗传平衡定律(P>0.05),所选取的研究对象具有群体代表性。CYP2C9基因分型结果显示,野生型CYP2C9*1/*1占92.1%(1 225例),杂合突变型CYP2C9*1/*2占0.5%(6例),杂合突变型CYP2C9*1/*3占7.3%(97例)和杂合突变型CYP2C9*2/*3占0.1%(2例)。CYP2C9*1、CYP2C9*2和CYP2C9*3 3种等位基因的频率分别为96.0%、0.3%和3.7%。男性和女性之间CYP2C9基因型(P=0.94)和等位基因频率(P=0.28)分布比较,差异无统计学意义。VKORC1-1639G>A基因分型检测结果显示,野生型VKORC1-1639GG占1.7%(22例),杂合突变型VKORC1-1639GA占19.7%(262例)和纯合突变型VKORC1-1639AA占78.6%(1 046例)。VKORC1-1639G>A位点G和A 2种等位基因频率分别为11.5%和88.5%。男性和女性之间VKORC1-1639G>A基因型(P=0.63)和等位基因频率(P=0.34)分布比较,差异无统计学意义。结论 中国南方客家人群CYP2C9和VKORC1-1639G>A基因遗传多态性与中国不同地区汉族人群和少数民族之间存在差异。基因分型检测可为指导梅州地区客家人群华法林个体化用药治疗提供重要分子遗传依据。Objectives To investigate the distribution of genetic polymorphisms of warfarin drug metabolism-related genes cytochrome P450 family 2 subfamily C polypeptide(CYP2C9)and vitamin K epoxide reductase subunit(VKORC1)-1639G>A in a Southern Chinese Hakka population.Methods Between July 2015 and January 2019,1330 out-and in-patients who received warfarin anticoagulant therapy orally were enrolled from the Meizhou People′s Hospital in this study.Genotyping of CYP2C9 and VKORC1-1639G>A polymorphisms was performed by polymerase chain reaction(PCR)amplification and microarray method.Genotype and allele frequencies of CYP2C9 and VKORC1-1639G>A in Hakka population in Southern China were compared to those published previously in other race in different regions.Results The genotype frequencies were in accordance with Hardy-Weinberg Equilibrium(P>0.05),which shown that the studied population were representative.Among the CYP2C9 genotyping results,the wild-type CYP2C9*1/*1 accounted for 92.1%(1225 cases),the heterozygous mutant CYP2C9*1/*2 accounted for 0.5%(6 cases),the heterozygous mutant CYP2C9*1/*3 accounted for 7.3%(97 cases),and the heterozygous mutant CYP2C9*2/*3 accounted for 0.1%(2 cases).The frequencies of the CYP2C9*1,CYP2C9*2 and CYP2C9*3 allele were 96.0%,0.3%and 3.7%,respectively.There were no statistically differences in CYP2C9 genotypes(P=0.94)and allele frequencies(P=0.28)between the male and female.Among the VKORC1-1639G>A genotyping results,the wild-type VKORC1-1639GG accounted for 1.7%(22 cases),the heterozygous mutant VKORC1-1639GA accounted for 19.7%(6 cases),and the homozygous mutant VKORC1-1639AA accounted for 78.6%(1046 cases).The frequencies of the G and A allele of VKORC1-1639G>A locus were 11.5%and 88.5%,respectively.There were no statistically differences in VKORC1-1639G>A genotypes(P=0.63)and allele frequencies(P=0.34)between the male and female.Conclusions Genetic polymorphisms of CYP2C9 and VKORC1-1639G>A genes in a Southern Chinese Hakka population are different from those of Chinese Han popula

关 键 词：CYP2C9 VKORC1-1639G>A 基因多态性 华法林 客家人群 

分 类 号：R973.2[医药卫生—药品]