CYP2C9基因多态性对苯妥因体内代谢的影响  

Effects of CYP2C9 Genotype on Phenytoin Metabolism

作　　者：任浩洋[1] 常红霞[1] 文思远[1] 

机构地区：[1]中国人民解放军总医院西院药局,北京100853

出　　处：《科学技术与工程》2008年第8期1976-1979,共4页Science Technology and Engineering

摘　　要：研究了CYP2C9基因多态性对苯妥因代谢活性的影响。采用PCR扩增及直接测序的方法检测65名健康受试者CYP2C9基因型。并利用高效液相色谱考察了野生型CYP2C9＊1／＊1携带者和杂合突变型CYP2C9＊1／＊3携带者对苯妥英代谢的影响。结果检测到5名健康志愿者携带CYP2C9＊3突变型等位基因（1075位碱基A—C），为CYP2C9＊1／＊3杂合突变型，未检测到CYP2C9＊4（1076位碱基T—C）和CYP2C9＊5（1080位碱基C—G）突变型等位基因。在受检人群中，未检测纯合突变型等位基因携带者。实验结果表明，CYP2C9基因型与p-HPPH／苯妥因代谢率之间具有显著的相关性。野生基因型携带者的平均代谢率为携带CYP2C9＊1／＊3杂合型等位基因志愿者的2倍以上，且两种基因型携带者间的代谢率具有统计学上的显著性差异。对本次健康受试者的CYP2C9基因型与苯妥因代谢的相关性研究表明，CYP2C9＊3突变型等位基因引起酶活性降低，对苯妥因的代谢减慢，与CYP2C9野生型相比具有显著性差异。由于中国人群中CYP2C9＊3（1075A—C）的发生频率较高，约为8％-10％。因此，当CYP2C9在药物代谢中起主要作用时应检测其CYP2C9＊3突变型。To investigate the effect of CYP2C9 polymorphism on phenytoin metabolism, PCR and direct se- quencing were used to detect genotype the CYP2C9 gene of 65 unrelated healthy volunteers. And the influence of genotypes of wildtype CYP2C9 ＊ 1/＊ 1 and heterozygous mutant CYP2C9 ＊ 1/＊ 3 on the phenytoin metabolism was also investigated using high performance liquid chromatography （HPLC）. 5 healthy volunteers were detected as carriers of CYP2C9 ＊ 3 mutant allele （1075A-C）, as heterozygous mutant CYP2C9 ＊ 1/＊ 3, no mutant alleles of CYP2C9 ＊4（1076T-C） and CYP2C9 ＊ 5（1080C-G） as detected. And no homozygous mutant was detected in the studied subjects. It was shown that the mean metabolic rate of phenytoin in wildtype CYP2C9 ＊ 1/＊ 1 carriers ware 2 times higher than that of heterozygous mutant CYP2C9 ＊ 1/＊ 3 carriers, and this was a statistically significant difference. The present association study of the CYP2C9 genotype and phenytoin metabolism showed that CYP2C9 ＊ 3 mutant allele induces a decreased enzymatic activity and slow metabolism of phenytoin, which was in significant difference when compared with CYP2C9 wild type. The incidence of the CYP2C9 ＊ 3 （1075A-C） in Chinese population is rather high, about 8% - 10%, therefore, CYP2C9 ＊ 3 mutant allele should be detected whenever CYP2C9 plays an important role in drug metabolism.

关 键 词：细胞色素P450 2C9 基因分型 苯妥因 药物代谢 个体差异 

分 类 号：R969.1[医药卫生—药理学]