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Parkinsonism Relat Disord. 2018 Aug;53:70-75. doi: 10.1016/j.parkreldis.2018.05.003. Epub 2018 May 9.

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

Author information

1
Department of Translational Science & Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
2
Center for Health and Technology, Department of Neurology, University of Rochester, Rochester, NY, USA.
3
Department of Neurology and Ophthalmology, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
4
Department of Translational Science & Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA; Department of Neurology, Washington University, Saint Louis, MO, USA.
5
Department of Translational Science & Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA; Mercy Health Saint Mary's, Grand Rapids, MI, USA.
6
Department of Translational Science & Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA; Mercy Health Saint Mary's, Grand Rapids, MI, USA. Electronic address: caryl.sortwell@hc.msu.edu.

Abstract

INTRODUCTION:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSIONS:

Data from two distinct, unmedicated, early-stage PD cohorts suggest that carrying two copies of the rs6265 Met66 allele (∼4% of the population) is associated with less severity in motor symptoms and potentially a slower rate of progression.

KEYWORDS:

Brain-derived neurotrophic factor; Levodopa; Single nucleotide polymorphism; Val66Met; rs6265

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