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

Single nucleotide polymorphisms (also known as SNPs) describe common genetic variation and can be used to tag regions across the human genome. When SNPs tag regions near to known genes they can help give clues as to how that gene might affect a given disease.   

It is interesting that variation at this SNP (called rs6265) is associated with slower progression in Parkinson's disease because it is near to the BDNF gene whose protein product influences the growth of nerve cells. The very same SNP (rs6265) is also associated with an number of the protective factors for Parkinson's such as smoking, body mass index and coffee consumption...

Coincidence... probably not...

- Alastair Noyce

Parkinsonism Relat Disord. 2018 May 9. pii: S1353-8020(18)30232-3. doi: 10.1016/j.parkreldis.2018.05.003. [Epub ahead of print]

Fischer DL, Auinger P, Goudreau JL, Paumier KL, Cole-Strauss A, Kemp CJ, Lipton JW, Sortwell CE.

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.