细胞色素P4502D6*10/*15基因多态性指导曲马多临床用药的分析  

Analysis of the cytochrome P4502D6*10/*15 gene polymorphism guided the clinical application of tramadol

作　　者：林美花 吴梅佳 顾梦洁 开洁静 黄倩 刘雪玲 饶跃峰[1,2] 赵青威 LIN Mei-hua;WU Mei-jia;GU Meng-jie;KAI Jie-jing;HUANG Qian;LIU Xue-ling;RAO Yue-feng;ZHAO Qing-wei(Research Center of Clinical Pharmacy,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,Zhejiang Province,China;Zhejiang Provincial Key Laboratory far Drug Evaluation and Clinical Research,Hangzhou 310003,Zhejiang Province,China)

机构地区：[1]浙江大学医学院附属第一医院临床药学研究中心,浙江杭州310003 [2]浙江省药物临床研究与评价技术重点实验室,浙江杭州310003

出　　处：《中国临床药理学杂志》2022年第7期639-642,共4页The Chinese Journal of Clinical Pharmacology

基　　金：浙江省自然科学基金资助项目(LQ20H160022);浙江省卫生健康委基金资助项目(2020RC009)。

摘　　要：目的基于临床案例探讨细胞色素P4502D6(CYP2D6)*15等位基因突变对曲马多用药的指导意义。方法基于荧光聚合酶链反应-毛细管电泳法检测CYP2D6基因第1外显子区的单核苷酸多态性(SNP)情况。进一步地通过检索遗传药理学知识库(PharmGKB)中CYP2D6等位基因分布频率、酶活性及临床功能状态等信息确证该患者基因型和表型。结果患者CYP2D6基因携带有1个活性降低的*10拷贝,1个无功能活性的*15拷贝及功能尚未明确的*43拷贝。结论该患者携带有*10/*15二倍体多态性,属于中间代谢型,理论上认为常规剂量曲马多体内活性代谢产物转化效率较低,治疗可能达不到预期疗效。Objective To investigate the significance of cytochrome P4502 D6(CYP2D6)*15 allele mutation on the clinical application of tramadol based on the case study.Methods The real-time polymerase chain reaction-capillary electrophoresis was applied to detect the single nucleotide polymorphism(SNP)in exon1 of CYP2D6 gene.Furthermore,the genotype and phenotype of the patient were confirmed based on the pharmacogenomics knowledge base(PharmgKB)regarding with the distribution frequency,enzyme activity and clinical functional status of the CYP2D6 allele.Results The patient carried one*10 copy of CYP2D6 gene with reduced activity,one*15 copy with no functional activity,and one*43 copy with undefined function.Conclusion The patient carried CYP2D6*10/*15 diploid,which belonged to the intermediate metabolic type.Theoretically,it was believed that the conversion efficiency of active metabolites in vivo with routine dose of tramadol was low,and the treatment might not achieve the expected efficacy.

关 键 词：曲马多 细胞色素P4502D6 荧光聚合酶链反应-毛细管电泳法 二倍体 

分 类 号：R971[医药卫生—药品]