Advances in understanding genomic markers and pharmacogenetics of Parkinson’s disease

<b>Introduction</b>: The inheritance pattern of Parkinson’s disease (PD) is likely multifactorial (owing to the interplay of genetic predisposition and environmental factors). Many pharmacogenetic studies have tried to establish a possible role of candidate genes in PD risk. Several studies have focused on the influence of genes in the response to antiparkinsonian drugs and in the risk of developing side-effects of these drugs. <b>Areas covered</b>: This review presents an overview of current knowledge, with particular emphasis on the most recent advances, both in case-control association studies on the role of candidate genes in the risk for PD as well as pharmacogenetic studies on the role of genes in the development of side effects of antiparkinsonian drugs. The most reliable results should be derived from meta-analyses of case-control association studies on candidate genes involving large series of PD patients and controls, and from genome-wide association studies (GWAS). <b>Expert opinion</b>: Prospective studies of large samples involving several genes with a detailed history of exposure to environmental factors in the same cohort of subjects, should be useful to clarify the role of genes in the risk for PD. The results of studies on the role of genes in the development of side-effects of antiparkinsonian drugs should, at this stage, only be considered preliminary.

**引言**：帕金森病（Parkinson’s disease, PD）的遗传模式大概率属于多因素致病，源于遗传易感性与环境因素的相互作用。诸多药物遗传学研究试图明确候选基因在帕金森病发病风险中可能发挥的作用。另有多项研究聚焦于基因对帕金森病治疗药物应答效果的影响，以及此类药物不良反应的发生风险。
**涵盖领域**：本综述对当前相关研究进展进行了系统性梳理，重点聚焦于最新研究成果，既涵盖了探讨候选基因与帕金森病发病风险关联的病例对照关联研究，也包含了分析基因对帕金森病治疗药物不良反应发生影响的药物遗传学研究。其中最具可靠性的研究结果，应来自针对候选基因的病例对照关联研究的荟萃分析（纳入大样本量的帕金森病患者与对照人群），以及全基因组关联研究（Genome-Wide Association Studies, GWAS）。
**专家观点**：针对纳入同一队列的大样本受试者开展前瞻性研究，同步检测多个基因的多态性并详细记录其环境暴露史，将有助于明确基因在帕金森病发病风险中的作用。而就帕金森病治疗药物不良反应相关的基因作用研究而言，现阶段其研究结果仅可视为初步结论。