浙江省汉族人群CYP2C19基因多态性与阿米替林代谢相关性分析  

Association between CYP2C19 gene polymorphism and amitriptyline metabolism of Han nationality in Zhejiang

作　　者：韩祺炜 易成[1] 李亚芳[1] 徐晶 HAN Qiwei;YI Cheng;LI Yafang(Department of Pharmaceutical,Hangzhou First People's Hospital,Hangzhou 310006,China)

机构地区：[1]杭州市第一人民医院药学部,浙江杭州310006 [2]解放军联勤保障部队第903医院药剂科

出　　处：《全科医学临床与教育》2020年第9期785-787,共3页Clinical Education of General Practice

摘　　要：目的探讨浙江省汉族人群细胞色素P4502C19(CYP2C19)基因多态性与阿米替林代谢的相关性。方法选取510名汉族浙江籍志愿者,采用突变扩增系统-聚合酶链反应(ARMS-PCR)方法检测CYP2C19*2、*3基因多态性,根据基因型对代谢类型进行分类,用反相高效液相色谱法检测各代谢类型人群血浆中阿米替林及其代谢物去甲替林的总浓度。结果 510名受试者CYP2C19*2的GG、GA、AA三种基因型频率占比分别为49.02%、42.94%、8.04%,其G和A等位基因频率分别为70.49%和29.51%。CYP2C19*3的GG、GA、AA三种基因型频率占比分别为65.09%、30.00%、4.91%,其G和A等位基因频率分别为80.09%和19.91%。快、中、慢代谢型分布频率分别为28.04%、56.67%、15.29%。慢代谢型受试者血浆阿米替林浓度均高于中代谢型和快代谢型(t分别=7.77、13.16,P均<0.05),且中代谢型高于快代谢型(t=8.29,P<0.05)。慢代谢型受试者血浆去甲替林浓度均低于中代谢型和快代谢型(t分别=19.02、20.92,P均<0.05),且中代谢型低于快代谢型(t=7.85,P<0.05)。结论浙江省汉族人群CYP2C19基因多态性具有个体差异,阿米替林代谢与基因多态性密切相关。Objective To investigate the relationship between cytochrome P4502C19(CYP2C19)gene polymorphism and amitriptyline metabolism of Han nationality in Zhejiang Province.Methods A total of 510 Han nationality volunteers from Zhejiang province were selected to detect CYP2C19 by amplification reflex mutation system polymerase chain reaction(ARMS-PCR)*2,*3 gene polymorphism.The total plasma concentrations of amitriptyline and its metabolite nortriptyline were determined by RP-HPLC.Results The frequencies of GG,GA and AA genotypes in 510 subjects were 49.02%,42.94%,and 8.04%,respectively,and the frequencies of G and A alleles were 70.49%and 29.51%,respectively.The frequencies of GG,GA and AA genotypes of CYP2C19*3 accounted for 65.09%,30.00%and 4.91%respectively,and the frequencies of G and A alleles were 80.09%and 19.91%respectively.The distribution of fast,medium and slow metabolism types were 28.04%,56.67%and 15.29%respectively.The plasma concentration of amitriptyline in the slow metabolism type group was higher than that in the middle metabolism type group and the fast metabolism type group(t=7.77,13.16,P<0.05),and that of the middle metabolism type group was higher than the fast metabolism type group(t=8.29,P<0.05).The plasma concentration of norepinephrine in the slow metabolism group was lower than that in the middle metabolism type group and fast metabolism type group(t=19.02,20.92,P<0.05),and the plasma norepine concentration of the middle metabolism type group was lower than that of the fast metabolism type group(t=7.85,P<0.05).Conclusion There are individual differences in CYP2C19 gene polymorphism of Han nationality in Zhejiang province,and amitriptyline metabolism is closely related to gene polymorphism.

关 键 词：阿米替林 CYP2C19 基因多态性 代谢 汉族人群 

分 类 号：R969.1[医药卫生—药理学]