Purcaro Carlo, Vanacore Nicola, Moret Federica, Di Battista Maria Elena, Rubino Alfonso, Pierandrei Silvia, Lucarelli Marco, Meco Giuseppe, Fattapposta Francesco, Pascale Esterina
Department of Human Neurosciences, Sapienza University, Rome, Italy.
National Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, Italy.
Neurosci Lett. 2019 Jan 18;690:83-88. doi: 10.1016/j.neulet.2018.10.021. Epub 2018 Oct 11.
L-dopa-induced dyskinesias (LID) is a common motor side effect of levodopa therapy of Parkinson's disease (PD). The identified predictors may only partially account for the risk of developing LID and genetic factors may contribute to this variability. The present study is aimed to investigate whether polymorphisms in the dopamine transporter gene (DAT) are associated with the risk of developing LID. Genotyping of the 40-bp VNTR (rs28363170) and rs393795 (A/C) polymorphisms of the DAT gene was performed in a well-characterized cohort of 181 Italian PD patients in treatment with L-DOPA for 3 years or more. The results of our study show that there is no difference in dyskinesias prevalence among carriers of the two DAT gene polymorphisms. However, the combination of the two genotypes 10R/10R (rs28363170) and A carrier (rs393795) of the DAT gene reduces the risk of LID occurrence during long-term therapy with l-DOPA with respect to the PD subjects who did not carry these alleles (OR = 0.31; 95% CI, 0.09-0.88). Also based on a logistic regression analysis, the 10R/10R and the A carrier allele of the rs393795 polymorphisms of the DAT gene, could reduce the susceptibility to develop LID during levodopa therapy adjusted by demographical and clinical variables (OR = 0.19; 95% CI, 0.05-0.69). Additional studies further investigating the rs28363170 and rs393795 polymorphisms with LID in PD are needed to clarify their role in different ethnicities.
左旋多巴诱导的异动症（LID）是帕金森病（PD）左旋多巴治疗常见的运动副作用。已确定的预测因素可能仅部分解释LID发生风险，遗传因素可能导致这种变异性。本研究旨在调查多巴胺转运体基因（DAT）多态性是否与LID发生风险相关。对181名接受左旋多巴治疗3年或更长时间的意大利PD患者进行了DAT基因40bp可变数目串联重复序列（VNTR，rs28363170）和rs393795（A/C）多态性的基因分型。我们的研究结果表明，两种DAT基因多态性携带者的异动症患病率没有差异。然而，DAT基因的两种基因型10R/10R（rs28363170）和A携带者（rs393795）的组合相对于未携带这些等位基因的PD受试者，可降低长期左旋多巴治疗期间LID发生的风险（比值比[OR]=0.31；95%置信区间[CI]，0.09-0.88）。同样基于逻辑回归分析，DAT基因rs393795多态性的10R/10R和A携带者等位基因，在经人口统计学和临床变量调整后，可降低左旋多巴治疗期间发生LID的易感性（OR=0.19；95%CI，0.05-0.69）。需要进一步开展研究，在PD患者中进一步研究rs28363170和rs393795多态性与LID的关系，以阐明它们在不同种族中的作用。
