Chen Yongping, Ou Ruwei, Zhang Lingyu, Gu Xiaojing, Yuan Xiaoqin, Wei Qian-Qian, Cao Bei, Zhao Bi, Wu Ying, Shang Huifang
Department of Neurology, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, China.
National Clinical Research Center for Geriatric, West China Hospital, Sichuan University, Chengdu, China.
Front Neurosci. 2020 Sep 3;14:889. doi: 10.3389/fnins.2020.00889. eCollection 2020.
Impaired dopamine metabolism is associated with Parkinson's disease (PD). Considering the overlap in the clinical and pathological characteristics between PD and multiple system atrophy (MSA), we investigated the effect of five potential functional polymorphisms in dopamine metabolism-related genes on disease susceptibility, phenotypes, and responses to dopamine in a large sample of PD and MSA patients. A total of 1506 PD patients, 496 MSA patients, and 894 healthy controls were included in this study. Five variants (rs6356 in , rs921451 in , rs4680 in , rs1799836 in , and rs1611115 in ) were genotyped in all cases using Sequenom iPLEX Assay technology. After adjusting for gender and age at onset, except for rs921451, which was associated with an increased risk of MSA ( = 0.001, OR = 1.21), no significant differences were found in genotype distribution or minor allele frequencies for the other four variants between PD and MSA patients and healthy controls. In the subgroup analysis, rs921451 was associated with an increased risk for late-onset PD as well as for PD onset in males ( = 0.002 [OR = 1.13] = 0.003 [OR = 1.15], respectively). In addition, patients harboring the risk allele rs921451 required lower levodopa equivalent daily doses of dopaminergic medication than those without the risk allele (52.00 ± 21.31 mg/day, = 0.015). None of the five candidate functional variants is a major determinant of the risk for PD or MSA. The modified PD phenotypes associated with these variants requires further confirmation.
多巴胺代谢受损与帕金森病（PD）相关。鉴于PD与多系统萎缩（MSA）在临床和病理特征上存在重叠，我们在大量PD和MSA患者样本中研究了多巴胺代谢相关基因的五个潜在功能多态性对疾病易感性、表型及对多巴胺反应的影响。本研究共纳入1506例PD患者、496例MSA患者和894名健康对照。使用Sequenom iPLEX检测技术对所有病例的五个变异位点（分别位于 、 、 、 及 中的rs6356、rs921451、rs4680、rs1799836和rs1611115）进行基因分型。在调整发病时的性别和年龄后，除rs921451与MSA风险增加相关（ = 0.001，OR = 1.21）外，PD和MSA患者与健康对照之间的其他四个变异位点在基因型分布或次要等位基因频率上未发现显著差异。在亚组分析中，rs921451与晚发型PD以及男性PD发病风险增加相关（分别为 = 0.002 [OR = 1.13]和 = 0.003 [OR = 1.15]）。此外，携带风险等位基因rs921451的患者比不携带风险等位基因的患者所需的多巴胺能药物左旋多巴等效日剂量更低（52.00 ± 21.31 mg/天， = 0.015）。这五个候选功能变异位点均不是PD或MSA风险的主要决定因素。与这些变异相关的PD表型改变需要进一步证实。
