药物基因组学在帕金森病个体化治疗中的作用  

The role of pharmacogenomics in the personalization of Parkinson′s disease treatment

作　　者：严伟倩 王春喻[1] Yan Weiqian;Wang Chunyu(Department of Neurology,the Second Xiangya Hospital,Central South University,Changsha 410011,China)

机构地区：[1]中南大学湘雅二医院神经内科,长沙410011

出　　处：《中华神经科杂志》2022年第7期755-764,共10页Chinese Journal of Neurology

基　　金：国家自然科学基金青年基金(81801123);国家自然科学基金面上项目(81970201)。

摘　　要：帕金森病是一种常见的神经系统退行性疾病,药物治疗是帕金森病最主要的治疗手段。左旋多巴是治疗帕金森病的标准疗法,是帕金森病药物治疗中最有效的对症治疗药物。帕金森病患者的临床特征、病程以及药物治疗反应存在显著的个体化差异,不仅与疾病的进程和环境因素相关,遗传因素也发挥了相当大的作用。药物基因组学是根据患者的遗传学基础或其他分子机制的诊断来预测患者对药物治疗的反应,从而给患者提供最佳的治疗方案,包括给药时间、给药剂量以及药物选择。药物基因组学解释了药物药代动力学和药效学中60%~90%的变异性。药物基因组学的主要决定因素包括致病基因、机制基因、代谢基因、转运体基因和基因多效性。文中将总结多巴胺信号通路编码基因多态性对药物反应的影响及遗传多态性对多巴胺能药物治疗相关的并发症和预后的影响。Parkinson′s disease(PD)is a common neurodegenerative disorder,which has a highly effective pharmacological symptomatic treatment.Levodopa is the most effective drug available for the symptomatic treatment of PD and is the gold standard with which other therapies must be compared.There are significant individual differences in clinical features,disease course,and response to pharmacological treatment in PD patients,not only attributed to disease process and environmental factors,but also genetic factors.Pharmacogenomics,also known as personalized medicine,is the study of how genetic variations in a person′s genome affect their response to drug therapies,which contribute to apply the patient with the best treatment plan,including the timing of dosing,the dose administered,and the most appropriate drugs.Pharmacogenomics accounts for 60%-90%variability in drug pharmacokinetics and pharmacodynamics.Major determinants of the pharmacogenomic outcome include pathogenic,mechanistic,metabolic,transporter and pleiotropic genes.This article will summarize the impact of polymorphisms in genes encoding dopamine signaling pathway on drug response,and the impact of genetic polymorphisms on complications and prognosis associated with dopaminergic drug therapy.

关 键 词：帕金森病 药物基因组学 个体化治疗 基因多态性 并发症 

分 类 号：R742.5[医药卫生—神经病学与精神病学]