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- Title
Pharmacogenetic profile and the development of the dyskinesia induced by levodopa-therapy in Parkinson's disease patients: a population-based cohort study.
- Authors
dos Santos, Erinaldo Ubirajara Damasceno; da Silva, Isaura Isabelle Fonseca Gomes; Asano, Amdore Guescel C.; Asano, Nadja Maria Jorge; De Mascena Diniz Maia, Maria; de Souza, Paulo Roberto Eleutério
- 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.
- Subjects
PHARMACOGENOMICS; PARKINSON'S disease; RESTRICTION fragment length polymorphisms; DYSKINESIAS; COHORT analysis; REGRESSION analysis
- Publication
Molecular Biology Reports, 2020, Vol 47, Issue 11, p8997
- ISSN
0301-4851
- Publication type
Article
- DOI
10.1007/s11033-020-05956-9