Szwedo Aleksandra A, Pedersen Camilla Christina, Ushakova Anastasia, Forsgren Lars, Tysnes Ole-Bjørn, Counsell Carl E, Alves Guido, Lange Johannes, Macleod Angus D, Maple-Grødem Jodi
The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.
Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway.
Front Neurol. 2021 Feb 10;11:620585. doi: 10.3389/fneur.2020.620585. eCollection 2020.
To evaluate the impact of polymorphisms originally identified as risk factors for Parkinson's disease (PD) on the clinical presentation and progression of the disease in a large cohort of population-based patients with incident PD. Four hundred thirty-three patients and 417 controls from three longitudinal cohorts were included in the study. Disease progression was recorded annually for up to 9 years using the Unified Parkinson's Disease Rating Scale (UPDRS) or Mini-Mental State Examination. Genotypes for five variants within the locus (rs2870004, rs356182, rs5019538, rs356219, and rs763443) were determined. We studied the association between each variant and disease progression using linear mixed-effects regression models. The clinical profile of the patients with PD at the point of diagnosis was highly uniform between genotype groups. The rs356219-GG genotype was associated with a higher UPDRS II score than A-allele carriers (β = 1.52; 95% confidence interval 0.10-2.95; = 0.036), but no differences were observed in the rate of progression of the UPDRS II scores. rs356219-GG was also associated with a faster annual change in Mini-Mental State Examination score compared with A-carriers (β = 0.03; 95% confidence interval 0.00-0.06; = 0.043). We show that the known PD-risk variant rs356219 has a minor effect on modifying disease progression, whereas no differences were associated with rs2870004, rs356182, rs5019538, and rs763443. These findings suggest that variants associated with PD risk may not be major driving factors to the clinical heterogeneity observed for PD.
为了评估最初被确定为帕金森病（PD）风险因素的基因多态性对一大群新发PD的基于人群的患者的临床表现和疾病进展的影响。该研究纳入了来自三个纵向队列的433例患者和417名对照。使用统一帕金森病评定量表（UPDRS）或简易精神状态检查表，每年记录疾病进展情况，最长记录9年。确定了该基因座内五个变体（rs2870004、rs356182、rs5019538、rs356219和rs763443）的基因型。我们使用线性混合效应回归模型研究了每个变体与疾病进展之间的关联。在基因型组之间，PD患者在诊断时的临床特征高度一致。rs356219-GG基因型与A等位基因携带者相比，UPDRS II评分更高（β = 1.52；95%置信区间0.10-2.95；P = 0.036），但在UPDRS II评分的进展速率上未观察到差异。与A等位基因携带者相比，rs356219-GG还与简易精神状态检查表评分的年度变化更快相关（β = 0.03；95%置信区间0.00-0.06；P = 0.043）。我们表明，已知的PD风险变体rs356219对改变疾病进展有较小影响，而rs2870004、rs356182、rs5019538和rs763443未观察到差异。这些发现表明，与PD风险相关的变体可能不是PD临床异质性的主要驱动因素。
