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Pharmacogenetic profile and the development of the dyskinesia induced by levodopa-therapy in Parkinson’s disease patients: a population-based cohort study

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Abstract

Levodopa-induced dyskinesia (LID) is an adverse effect that negatively impacts the quality of life of patients with Parkinson’s disease (PD). Studies report that genetic variations in the genes of the pharmacogenetic pathway of the levodopa (L-DOPA) might be associated with LID development. The goal of the present study was to investigate a possible influence of functional genetic variants in the DRD1 (rs4532), DRD2 (rs1800497), DAT1 (rs28363170), and COMT (rs4680) genes with LID development. A total of 220 patients with idiopathic PD were enrolled. The genotyping for DRD1 (rs4532), DRD2 (rs1800497), DAT1 (rs28363170), and COMT (rs4680) polymorphisms were performed using Restriction Fragment Length Polymorphism (PCR–RFLP). Univariate and multivariate analyses were performed to assess the association of these polymorphisms and risk factors with LID development. Multivariate Cox regression analysis showed increased risk to LID development for both Levodopa Dose Equivalency (LED) (Hazard ratios (HR) = 1.001; 95% CI 1.00–1.01; p = 0.009) and individuals carrying the COMT L/L genotype (HR = 2.974; 95% CI 1.12–7.83; p = 0.010). Furthermore, when performed a Cox regression analysis adjusted for a total LED, we observed that the genotype COMT L/L had a 3.84–fold increased risk for LID development (HR = 3.841; 95% CI 1.29–11.37; p = 0.012). Our results suggest that before treating LID in PD patients, it is important to take into consideration genetic variant in the COMT gene, since COMT LL genotype may increase the risk for LID development.

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Acknowledgement

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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Authors and Affiliations

  1. Graduate Program in Applied Cellular and Molecular Biology, University of Pernambuco (UPE), Rua Dom Manuel de Medeiros, S/N –Dois Irmãos, CEP:52171-900, Recife, PE, Brazil

    Erinaldo Ubirajara Damasceno dos Santos & Paulo Roberto Eleutério de Souza

  2. Graduate Program in Genetics, Federal University of Pernambuco (UFPE), Recife, PE, Brazil

    Isaura Isabelle Fonseca Gomes da Silva & Paulo Roberto Eleutério de Souza

  3. Department of Biology, Federal Rural University of Pernambuco (UFRPE), Recife, PE, Brazil

    Maria De Mascena Diniz Maia & Paulo Roberto Eleutério de Souza

  4. Department of Clinical Medicine, Faculty of Medicine, Federal University of Pernambuco (UFPE), Recife, PE, Brazil

    Amdore Guescel C. Asano & Nadja Maria Jorge Asano

  5. Pro-Parkinson Program of the Clinical Hospital of the Federal University of Pernambuco Recife (HC/UFPE), Recife, PE, Brazil

    Amdore Guescel C. Asano & Nadja Maria Jorge Asano

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  1. Erinaldo Ubirajara Damasceno dos Santos
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  2. Isaura Isabelle Fonseca Gomes da Silva
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Correspondence to Paulo Roberto Eleutério de Souza.

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dos Santos, E.U.D., da Silva, I.I.F.G., Asano, A.G.C. et al. Pharmacogenetic profile and the development of the dyskinesia induced by levodopa-therapy in Parkinson’s disease patients: a population-based cohort study. Mol Biol Rep 47, 8997–9004 (2020). https://doi.org/10.1007/s11033-020-05956-9

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