基因芯片法测定中国人群细胞色素P450 2D6的基因多态性  

Genetic polymorphism of cytochrome P450 2D6 in Chinese population detected by gene chips

作　　者：李芹[1] 王睿[2] 许力[3] 文思远[3] 王升启[3] 

机构地区：[1]中国海洋大学海洋药物与食品研究所,山东省青岛市266003 [2]解放军总医院临床药理室,北京市100853 [3]解放军军事医学科学院放射医学研究所,北京市100850

出　　处：《中国临床康复》2006年第24期39-41,共3页Chinese Journal of Clinical Rehabilitation

基　　金：国家"八六三"计划支持项目(2004AA2Z3765)~~

摘　　要：目的:根据细胞色素P4502D6基因序列的多态性分布特点,针对在中国人群药物代谢中具有潜在作用的突变位点C188T和G4268C,设计寡核苷酸探针,制备寡核苷酸芯片,探讨基因芯片技术应用于CYP2D6基因分型的可行性,观察中国人群细胞色素P4502D6的基因多态性。方法:实验于2005-02/08进行。以克隆并已测序的细胞色素P4502D6基因重组质粒作为标准样品,扩增产物与芯片进行杂交,制备基因芯片,测定312名中国健康志愿者(已签署知情同意书)细胞色素P4502D6基因分型,并使用直接测序法对结果进行验证。结果:312名全部进入结果分析。①312名中国健康志愿者中CYP2D62和CYP2D610的变异频率分别为CYP2D62W10W8.3%,2H10W13.5%,2M10W10.6%,2M10H17.0%,2M10M34.6%,2H10H9.6%,2H10M6.4%。②对部分样本采用直接测序的方法进行进一步确证,结果完全吻合。结论:①CYP2D62和CYP2D610突变型等位基因在中国人群中出现的频率较高。②基因芯片法简便、快捷,适用于中国人群细胞色素P4502D6基因分型研究。AIM： To design oliganucleotide probe, prepare the oligonucleotide chip, explore the feasibility of gene chips for investigation the cytochromeP450 2D6 （CYP2D6） genotyping, and observe the CYP2D6 genetic polymorphism in Chinese population, according to the distributing feature of the genetic polymorphisms, and specially aimed at C188T and G4268C mutant sites, which are reported to have the potential effects in the drug metabolism of Chinese people. METHODS： The experiment was conduct from February to August 2005. CYP2D6 gene recombinant plasmid after cloning and sequencing was taken as master sample, and then the amplification products were hybridized with chips to prepare the gene chips. A total of 312 Chinese healthy volunteers （who signed the informed consents） were selected to determine CYP2D6 genotype. And the genotyping results were confirmed by direct sequencing. RESULTS： Totally 312 Chinese volunteers were involved in the result analysis. ① The allelic frequencies of CYP2D6 were 8.3% （CYP2D6＊2W＊10W）, 13.5% （＊2H＊10W）, 10.6% （＊2M＊10W）, 17.0% （＊2M＊10H）, 34.6% （＊2M＊10M）, 9.6% （＊2H＊10H） and 6.4% （＊2H＊10M）, respectively. ②Part of the samples verified by direct sequencing were completely consistent with the genotyping results by gene chips. CONCLUSION： ①CYP2D6＊2 and CYP2D6＊10 mutant alleles present frequently in Chinese population. ②Gene chip is convenient, rapid and reliable for the determination of CYP2D6 genetic polymorphisms in Chinese population.

关 键 词：细胞色素P450 CYP2D6/遗传学 多态现象(遗传学) 寡核苷酸序列分析 

分 类 号：R394[医药卫生—医学遗传学]