2467例中国汉族患者CYP2D6基因多态性分布频率研究  

Study on the distribution frequency of CYP2D6 gene polymorphism in 2467 Han Chinese patients

作　　者：孙亚红[1] 林阳[1] 石秀锦[1] SUN Ya-hong;LIN Yang;SHI Xiu-jin(Department of Pharmacy,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院药事部,北京100029

出　　处：《临床药物治疗杂志》2023年第6期36-40,共5页Clinical Medication Journal

基　　金：国家重点研发计划“精准医学研究”重点专项(2017YFC0908801)。

摘　　要：目的 回顾性分析CYP2D6基因多态性在中国汉族人群中的分布情况,探讨CYP2D6基因检测对其敏感底物药物美托洛尔、他莫昔芬、可待因代谢的意义。方法 对2018年12月至2020年1月在首都医科大学附属北京安贞医院完成CYP2D6基因型检测的门诊和住院患者进行汇总分析。结果 共有2479例服用美托洛尔的患者进行了CYP2D6基因型检测,其中少数民族患者12例,汉族患者2467例。汉族人群最常见等位基因型是野生型^(*)1、活性无改变的突变型^(*)2和酶功能降低的突变^(*)10;主要的双倍型是^(*)1/^(*)10(37.9%)、^(*)10/^(*)10(27.7%)和^(*)1/^(*)1(25.0%)。检测结果显示,无超快代谢型和慢代谢型患者,正常代谢型患者占比高达72.1%,而CYP2D6^(*)10/^(*)10基因型的中间代谢型患者占比高达27.7%。结论 中国汉族人群CYP2D6基因型分布有自身的特色,中国汉族人群CYP2D6基因型以正常代谢型为主,超快代谢型或慢代谢型罕见,而中间代谢型可能是汉族人群CYP2D6酶活性降低的主要原因,在应用经CYP2D6代谢灭活(如美托洛尔)或代谢活化(如他莫昔芬、可待因)的药物时,应该关注^(*)10/^(*)10等位基因突变带来的疗效和安全性问题。Objective To retrospectively investigate the distribution of CYP2D6 gene polymorphism in the Han Chinese population,and to explore the significance of CYP2D6 gene detection in the metabolism of sensitive substrates such as metoprolol,tamoxifen,and codeine.Methods A summary analysis was conducted on outpatient and inpatient patients who completed CYP2D6 genotype testing at Beijing Anzhen Hospital from December 2018 to January 2020.Results A total of 2479 patients taking metoprolol underwent CYP2D6 genotype testing,including 12 minority patients and 2467 Han patients;the most common alleles in the Han population are wild-type ^(*)1,mutated type ^(*)2 with unchanged activity,and mutated type ^(*)10 with reduced enzyme function.The main diploids are ^(*)1/^(*)10(37.9%),^(*)10/^(*)10(27.7%),and ^(*)1/^(*)1(25.0%).Test results showed that there were no ultrarapid or poor metabolizer and the proportion of normal metabolism patients was as high as 72.1%,while the proportion of intermediate metabolism patients with CYP2D6 ^(*)10/^(*)10 genotype was as high as 27.7%.Conclusion The distribution of CYP2D6 genotypes in the Han Chinese population has its own characteristics,the CYP2D6genotype in the Chinese Han population is mainly characterized by normal metabolizer,while ultrarapid or poor metabolizer are rare.The intermediate metabolizer may be the main reason for the decrease in CYP2D6 enzyme activity in the Han population.When using certain drugs that have been metabolically inactivated by CYP2D6(metoprolol) or metabolically activated(tamoxifen and codeine),attention should be paid to the efficacy and safety issues caused by ^(*)10/^(*)10 allele mutations.

关 键 词：CYP2D6 基因多态性 中间代谢型 美托洛尔 

分 类 号：R969.3[医药卫生—药理学]