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Influence of DRD1 and DRD3 Polymorphisms in the Occurrence of Motor Effects in Patients with Sporadic Parkinson’s Disease

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Abstract

Parkinson’s disease (PD) is a multisystem disorder that affects 2–3% of the population ≥ 65 years of age. The main pharmacologic agent use in the treatment of clinical symptoms of PD is levodopa (L-DOPA). However, the chronic use of L-DOPA might result in the emergence of motor complications such as motor fluctuation and dyskinesia. Previous studies have shown that the inter-individual variability and pharmacogenetic profile of PD patients seem to influence the occurrence of motor complications. For these reasons, the purpose of this study was to evaluate a possible relationship between DRD1 A48G and DRD3 Ser9Gly genetic variants with the occurrence of motor complications in PD patients in a Brazilian population. A total of 228 patients with idiopathic PD were enrolled. Patients were genotyped for DRD1 A48G and DRD3 Ser9Gly polymorphisms using PCR–RFLP. The univariate and multivariate analyses were performed to assess the association of these polymorphisms with the occurrence of motor fluctuation and dyskinesia in PD patients. Multiple Poisson regression analyses showed a protector effect to the occurrence of dyskinesia for individuals carrying of the DRD1 G/G genotype (PR 0.294; CI 0.09–0.87; p ≤ 0.020) after the threshold Bonferroni’s. Besides, we verified risk increased to the occurrence of motor complications with daily L-DOPA dosage, disease duration, and users of rasagiline, selegiline, or entacapone (p < 0.05 for all). Our results suggest that the DRD1 A48G polymorphism and the presence of extrinsic and intrinsic factors may role an effect in the occurrence of dyskinesia in PD patients.

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Acknowledgements

We thank the patients and their families, whose collaboration and understanding have made this work possible.

Funding

This study was supported by the Brazilian funding agency FACEPE (Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco) and in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.

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Correspondence to Paulo Roberto Eleutério de Souza.

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The authors declare that they have no conflicts of interest and no competing financial interests.

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dos Santos, E.U.D., Duarte, E.B.C., Miranda, L.M.R. et al. Influence of DRD1 and DRD3 Polymorphisms in the Occurrence of Motor Effects in Patients with Sporadic Parkinson’s Disease. Neuromol Med 21, 295–302 (2019). https://doi.org/10.1007/s12017-019-08549-3

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  • DOI: https://doi.org/10.1007/s12017-019-08549-3

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