Session Information
Date: Wednesday, June 7, 2017
Session Title: Parkinson's Disease: Genetics
Session Time: 1:15pm-2:45pm
Location: Exhibit Hall C
Objective: To determine whether the GBA polymorphism T369M is associated with earlier age of onset, lower cognitive performance, and more severe motor impairment in Parkinson’s disease (PD).
Background: PD is a heterogeneous disease with variable age of onset and rates of motor and cognitive progression. GBA mutations and the E326K polymorphism are risk factors for PD, and among PD patients those who carry these variants exhibit a more rapid decline in motor and cognitive function. A recent meta-analysis of case-control studies concluded that another GBA polymorphism,T369M, is a PD risk factor. However, whether T369M is associated with worse motor and cognitive function is not yet known.
Methods: In this cross-sectional study, we sequenced the entire GBA coding region in 1743 PD patients from 10 sites in the PD Cognitive Genetics Consortium. Patients underwent assessments of global cognitive abilities (Montreal Cognitive Assessment), language processing (semantic and phonemic verbal fluency), learning and memory (Hopkins Verbal Learning Test-Revised), working memory/executive function (Letter-Number Sequencing Test and Trail Making Test A and B), and visuospatial ability (Benton Judgment of Line Orientation). Motor function was assessed using the MDS-UPDRS III scale. We used linear regression to test for association between T369M and MDS-UPDRS III scores and cognitive performance, and logistic regression to assess the proportion of subjects with dementia. We adjusted for important covariates, including site, sex, age at testing, disease duration, education (cognitive data only) and levodopa equivalent dose (motor only). Individuals who carried a GBA mutation or E326K were excluded from analysis.
Results: Thirty-eight patients (2.2%) carried T369M. There was no significant association between genotype and age at onset (p=0.06), MDS-UPDRS III score (p=0.53), proportion of subjects with dementia (p=0.14), or performance on any of the cognitive tests (Table 1).
Conclusions: Our data suggest that unlike GBA mutations and E326K, the T369M polymorphism is likely not associated associated with a more severe PD phenotype. This information will be important in selecting patients for participation in future clinical trials focused on GBA-related Lewy body disorders.
To cite this abstract in AMA style:
A. Julius, Y.-H. Lin, M. Smith, J. Leverenz, D. Weintraub, J. Trojanoswski, V. Van Deerlin, B. Ritz, R. Rausch, J. Quinn, K. Chung, S. Factor, L. Rosenthal, T. Dawson, M. Albert, A. Espay, F. Revilla, J. Devoto, J. Goldman, G. Stebbins, B. Bernard, Z. Zbigniew, O. Ross, D. Dickson, D. Yearout, S.-C. Hu, C. Johnson, B. Cholerton, T. Montine, K. Edwards, C. Zabetian. Association of the GBA T369M polymorphism with motor and cognitive symptoms in Parkinson’s disease [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/association-of-the-gba-t369m-polymorphism-with-motor-and-cognitive-symptoms-in-parkinsons-disease/. Accessed June 15, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/association-of-the-gba-t369m-polymorphism-with-motor-and-cognitive-symptoms-in-parkinsons-disease/