Objective: To examine the association between dyskinesia and haplotypes in the genes of three dopamine receptors (DRD1, DRD2 and DRD3) and of the Brain Derived Neurotrophic Factor (BDNF).

Background: Dyskinesia is a known side-effect of levodopa treatment of Parkinson’s Disease (PD). While some patients develop dyskinesia early in their disease, there are exceptions of patients who never develop dyskinesia even when treated with high doses of levodopa. The DRD and BDNF loci have been hypothesized to influence the development of dyskinesia.

Methods: Patient data was drawn from a population-based case-control study, the Parkinson’s Environment and Gene study. We included 418 patients with: a confirmed diagnosis by a movement disorder specialist, levodopa treatment, and a minimum three years disease duration at the time of assessment. Applying Haploview and Phase, we created a single haploblock for DRD1 and BDNF, and three haploblocks for DRD2 and DRD3. We generated risk scores for DRD2 and DRD3, and used Poisson regression with robust error variance to estimate risk ratios

Results: There was no difference in dyskinesia prevalence among carriers of haplotypes in DRD1 nor BDNF. In each of the DRD2 haploblocks, there was one haplotype that was associated with a 29% to 50% increase in the risk of developing dyskinesia compared to the reference haplotype. Each unit increase in our DRD2 risk score was associated with a 16% increase in dyskinesia risk (95%CI: 1.05-1.29). For the DRD3 haploblocks, there might be an association between some haplotypes and dyskinesia although the confidence intervals included the null. Each unit increase in our DRD3 risk score was associated with a 17% increase in dyskinesia risk (95%CI: 0.99-1.40). While the BDNF haploblock was not associated, the minor allele of the rs6265 SNP was associated with dyskinesia (adjusted RR 1.31 (95%CI: 1.01-1.70)).

Conclusions: Carriers of DRD2, and potentially DRD3, risk haplotypes had an increased risk of developing dyskinesia. Thus, the DRD2 gene appears to be involved in pathomechanisms leading to the development of dyskinesia. Furthermore, the DRD3 and BDNF gene might also influence dyskinesia prevalence. PD patients with these DRD2 risk haplotypes would be prime candidates for treatments that aim to prevent or delay the onset of dyskinesia.

* This abstract has been presented as a poster during the World Parkinson Congress on September 23, 2016.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-variants-influencing-dyskinesia-potential-consequences-for-treatment-in-parkinsons-disease/