三维凝胶基因芯片法研究中国人群CYP2C9与CYP2C19基因多态性  

Study on the CYP2C9 and CYP2C19 genetic polymorphism in Chinese subjects by using 3-dimense polyacrylamide gel-based microarray platform

作　　者：马晶晶[1] 李金恒[1] 程璐[2] 

机构地区：[1]南京大学医学院临床学院南京军区南京总医院药理科 [2]东南大学国家生物电子学重点实验室

出　　处：《中国临床药理学与治疗学》2009年第9期966-973,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金资助项目(No30472055)

摘　　要：目的:应用三维凝胶基因芯片方法研究中国人群CYP2C9与CYP2C19基因多态性,为临床合理用药提供新的技术手段与研究方法。方法:提取207名男性健康志愿者基因组DNA,PCR分别扩增包含CYP2C9*3、*13与CYP2C19*2、*3多态位点目标片段,制备三维凝胶基因芯片,荧光标记探针杂交,芯片扫描并基因分型,用直接测序法对结果进行验证。结果:207人中,11人为CYP2C9*1/*3基因型,1人为CYP2C9*1/*13基因型,1人为CYP2C9*3/*3基因型。2C9*3、*13等位基因发生率分别为2.90%、0.24%,慢代谢型发生率为0.48%。CYP2C19突变杂合子有97人,突变纯合子有26人,2C19*2、*3等位基因发生率分别为32.85%、3.62%,慢代谢型发生率为12.56%。四种等位基因型分布均符合Hardy-Weinberg平衡。结论:三维凝胶基因芯片方法可为临床快速基因分型提供高效平台。CYP2C9与CYP2C19基因在中国人群存在普遍多态性,检测其基因型可有效指导相关临床治疗药物应用,提高药效,降低不良反应。AIM： To study the genetic polymorphisms of CYP2C9 and CYP2C19 by using 3-dimense polyacrylamide gel-based microarray method in healthy male Chinese subjects,providing original technology and research method for clinical rational administration.METHODS：207 healthy male Chinese volunteers were recruited and their genomic DNA were isolated.The genomic fragments containing CYP2C9＊3,＊13 and CYP2C19＊2,＊3 polymorphic sites were amplified respectively to prepare 3-dimense polyacrylamide gel-based microarrays.After hybridized by fluorescent labeling probes,the microarrays were scanned to obtain genotyping results of CYP2C9 and CYP2C19.The analytic results were confirmed by direct sequencing.RESULTS： In 207 volunteers,the number of subjects with CYP2C9＊1/＊3,CYP2C9＊1/＊13 and CYP2C9＊3/＊3 genotype were 11,1,and 1,respectively.The frequencies of CYP2C9＊3 and CYP2C9＊13 alleles were 2.90% and 0.24%,respectively.The incidence of CYP2C9 poor metabolizers was 0.48%.With regard to CYP2C19,heterozygous variants were 97 and homozygous variants were 26.The frequencies of CYP2C19＊2 and CYP2C19＊3 alleles were 32.85% and 3.62%,respectively.The incidence of CYP2C19 poor metabolizers was 12.56%.The distribution of the four alleles were all coincident with Hardy-Weinberg law.CONCLUSION：3-dimense polyacrylamide gel-based microarray method could serve as an advanced platform for clinical genotyping.The polymorphisms of CYP2C9 and CYP2C19 are frequent in Chinese population.Detecting the Genotyping CYP2C9 and CYP2C19 gene before administration could optimize related clinical drugs therapy,with the purpose of high efficiency and low incidence of adverse reactions.

关 键 词：CYP2C9 CYP2C19 基因多态性 三维凝胶基因芯片 DNA纯化 

分 类 号：R969[医药卫生—药理学]