Polymorphisms in the dopamine transporter gene are associated with visual hallucinations and levodopa equivalent dose in Brazilians with Parkinson's disease

The requirement for dopaminergic drugs in Parkinson's disease (PD) is highly variable. Visual hallucinations are a frequent and serious complication of chronic levodopa therapy. Polymorphisms in the DAT1 gene might affect the reuptake of dopamine in the synaptic cleft, but the influence of this variability on adverse effects or levodopa equivalent dose on PD patients is still poorly investigated. Therefore, the aim of the present study was to investigate DAT1 gene polymorphisms on levodopa equivalent dose and visual hallucination occurrence in PD patients. Altogether, 196 PD patients in treatment with at least 200 mg levodopa equivalent dose for at least 1 yr were included. These patients were genotyped for the -839 C>T and 3' VNTR DAT1 polymorphisms by PCR-based methodologies. Visual hallucinations occurred in 25.5% of the sample. After controlling for confounders, the dopamine transporter (DAT) -839 C allele was associated with visual hallucinations (prevalence ratio 2.5, 95% confidence intervals 1.13-5.5, p=0.02). Levodopa equivalent dose was lower in carriers of the nine repeat allele of the DAT 3'UTR VNTR (741.2 +/- 355.0 vs. 843.4 +/- 445.7), explaining 21% of dose variability (p=0.01). Our results support an effect of DAT1 polymorphisms in adverse effects of anti-Parkinsonian drugs and in levodopa equivalent dose usage.