Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients

Frontiers in Neurology

Johannes Lange¹  Jodi Maple-Grødem¹  Aleksandra A. Szwedo¹  Camilla Christina Pedersen¹  Ole-Bjørn Tysnes²  Lars Forsgren³  Guido Alves⁵  Carl E. Counsell⁶  Angus D. Macleod⁶  Anastasia Ushakova⁷ 

[1] Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway;Department of Clinical Medicine, University of Bergen, Bergen, Norway;Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden;Department of Neurology, Haukeland University Hospital, Bergen, Norway;Department of Neurology, Stavanger University Hospital, Stavanger, Norway;Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom;Section of Biostatistics, Department of Research, Stavanger University Hospital, Stavanger, Norway;The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway;

关键词: SNCA;    Parkinson's disease;    disease progression;    genetic association;    cognitive impairment;   

DOI  :  10.3389/fneur.2020.620585

来源: DOAJ

【 摘 要 】

Objectives: To evaluate the impact of SNCA 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.Methods: 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 SNCA 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.Results: 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; p = 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; p = 0.043).Conclusions: 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 SNCA variants associated with PD risk may not be major driving factors to the clinical heterogeneity observed for PD.

【 授权许可】

Unknown