Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients
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...
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doaj-d7c6874432634b83a381296084f195392021-02-10T09:36:57ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-02-011110.3389/fneur.2020.620585620585Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed PatientsAleksandra A. Szwedo0Aleksandra A. Szwedo1Camilla Christina Pedersen2Camilla Christina Pedersen3Anastasia Ushakova4Lars Forsgren5Ole-Bjørn Tysnes6Ole-Bjørn Tysnes7Carl E. Counsell8Guido Alves9Guido Alves10Guido Alves11Johannes Lange12Johannes Lange13Angus D. Macleod14Jodi Maple-Grødem15Jodi Maple-Grødem16The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, NorwayDepartment of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, NorwayThe Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, NorwayDepartment of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, NorwaySection of Biostatistics, Department of Research, Stavanger University Hospital, Stavanger, NorwayDepartment of Clinical Science, Neurosciences, Umeå University, Umeå, SwedenDepartment of Neurology, Haukeland University Hospital, Bergen, NorwayDepartment of Clinical Medicine, University of Bergen, Bergen, NorwayInstitute of Applied Health Sciences, University of Aberdeen, Aberdeen, United KingdomThe Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, NorwayDepartment of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, NorwayDepartment of Neurology, Stavanger University Hospital, Stavanger, NorwayThe Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, NorwayDepartment of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, NorwayInstitute of Applied Health Sciences, University of Aberdeen, Aberdeen, United KingdomThe Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, NorwayDepartment of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, NorwayObjectives: 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.https://www.frontiersin.org/articles/10.3389/fneur.2020.620585/fullSNCAParkinson's diseasedisease progressiongenetic associationcognitive impairment |
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English |
format |
Article |
sources |
DOAJ |
author |
Aleksandra A. Szwedo Aleksandra A. Szwedo Camilla Christina Pedersen Camilla Christina Pedersen Anastasia Ushakova Lars Forsgren Ole-Bjørn Tysnes Ole-Bjørn Tysnes Carl E. Counsell Guido Alves Guido Alves Guido Alves Johannes Lange Johannes Lange Angus D. Macleod Jodi Maple-Grødem Jodi Maple-Grødem |
spellingShingle |
Aleksandra A. Szwedo Aleksandra A. Szwedo Camilla Christina Pedersen Camilla Christina Pedersen Anastasia Ushakova Lars Forsgren Ole-Bjørn Tysnes Ole-Bjørn Tysnes Carl E. Counsell Guido Alves Guido Alves Guido Alves Johannes Lange Johannes Lange Angus D. Macleod Jodi Maple-Grødem Jodi Maple-Grødem Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients Frontiers in Neurology SNCA Parkinson's disease disease progression genetic association cognitive impairment |
author_facet |
Aleksandra A. Szwedo Aleksandra A. Szwedo Camilla Christina Pedersen Camilla Christina Pedersen Anastasia Ushakova Lars Forsgren Ole-Bjørn Tysnes Ole-Bjørn Tysnes Carl E. Counsell Guido Alves Guido Alves Guido Alves Johannes Lange Johannes Lange Angus D. Macleod Jodi Maple-Grødem Jodi Maple-Grødem |
author_sort |
Aleksandra A. Szwedo |
title |
Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients |
title_short |
Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients |
title_full |
Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients |
title_fullStr |
Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients |
title_full_unstemmed |
Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients |
title_sort |
association of snca parkinson's disease risk polymorphisms with disease progression in newly diagnosed patients |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2021-02-01 |
description |
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. |
topic |
SNCA Parkinson's disease disease progression genetic association cognitive impairment |
url |
https://www.frontiersin.org/articles/10.3389/fneur.2020.620585/full |
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