Bdnf variant is associated with milder motor symptom severity in early-stage Parkinson's disease

Parkinsonism & Related Disorders
D Luke FischerCaryl E Sortwell

Abstract

Parkinson's disease (PD) progression is heterogeneous. Variants in PD-related genes may alter disease progression or severity. We examined if the single nucleotide variant rs6265 in the gene Bdnf alters clinical phenotype in early-stage, unmedicated PD. A retrospective analysis was conducted using data collected in the Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) study. DNA samples (n = 217) were genotyped for the Bdnf rs6265 variant, and the primary endpoint was time to initiate levodopa. The Parkinson's Progression Markers Initiative (PPMI) was used for validation (n = 383). The primary endpoint of time to initiate levodopa was associated with a delay in subjects with two copies of the rs6265 minor (Met66) allele (HR: 4.9; 95% CI: 1.3-18.8). Secondary endpoints were not different among genotypes. PPMI subjects with two Met66 alleles demonstrated significantly lower total and part III Movement Disorder Society - United Parkinson's Disease Rating Scale (MDS-UPDRS) scores at baseline, as well as more tremor-related symptoms, but not a delay in initiation of maintenance pharmacotherapy. Data from two distinct, unmedicated, early-stage PD cohorts suggest that carrying two copies of the rs6265 Met66 allel...Continue Reading

Citations

Jun 25, 2019·Frontiers in Neurology·Yang JinSong Bai Xu
Nov 25, 2020·Journal of Molecular Neuroscience : MN·Tarapati RanaSimona Bungau
Nov 21, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·D Luke FischerCaryl E Sortwell
Jul 22, 2021·Neuromodulation : Journal of the International Neuromodulation Society·Caryl E SortwellP David Charles

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