L-Dopa-induced adverse effects in PD and dopamine transporter gene polymorphism

Objective: To assess whether polymorphisms in the dopamine receptor genes and in the dopamine transporter gene ( DAT ) are predictors of adverse effects of l -dopa. Methods: A retrospective noninterventional study with 183 patients with PD was conducted. Nine polymorphisms of the dopamine D2 receptor ( DRD2 ), two of the dopamine D3 receptor ( DRD3 ), three of the dopamine D4 receptor ( DRD4 ), and one variable number of tandem repeats (VNTR) of the DAT were studied. The entire coding and promoter regions of the DRD2 gene of 48 patients with early and severe appearance of adverse effects from l -dopa treatment and of eight never-afflicted patients were sequenced. Results: The polymorphisms of DRD2 , DRD3 , and DRD4 were not associated with the risk to develop adverse effects of l -dopa. However, patients with psychosis or dyskinesia carried the nine copy allele 40–bp VNTR of the DAT more frequently than nonafflicted patients (60.0 vs 36.8%, p = 0.008; and 54.7 vs 32.9%, p = 0.006). Sequencing of the DRD2 gene revealed no new mutation, with the exception of one silent mutation in exon 6. Conclusions: Genetic variations of the DRD2 , DRD3 , and DRD4 do not influence the occurrence of l -dopa-induced adverse effects. However, the nine copy allele 40–bp VNTR of the DAT is a predictor for the occurrence of psychosis or dyskinesia in l -dopa-treated patients.