Gene polymorphisms and motor levodopa-induced complications in Parkinson's disease

The aim of the study was to evaluate the association of individual and combined single-nucleotide polymorphisms in brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and catechol-O-methyltransferase (COMT) genes with the occurrence of motor levodopa-induced complications (MLIC) in Parkinson's disease (PD).

We studied 76 patients with PD (MLIC occurred in 56.6%) and 60 controls. Allelic discrimination of rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) genes were genotyped. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using multinominal logistic regression. Orthogonal partial least squares (OPLS) analysis and OPLS discriminant analysis (OPLS-DA) were used to analyze qualitative genetic data.

The risk of PD in subjects with the AG BDNF genotype was increased sixfold (OR = 6.12, 95% CI = 2.88-13.02, p < .0001), and AG BDNF and AG DAT genotypes were correlated with PD in OPLS-DA (VIP > 1). There were no differences in distributions of BDNF, DAT and COMT genotypes between PD groups with and without MLIC, while OPLS model showed that genotype combination of AG BDNF, AG DAT, and GG COMT was correlated with MLIC and genotypes combination of GG BDNF, AA DAT, and AA COMT with lack of MLIC in PD patients (VIP > 1).

Our results confirmed the association of rs6265 BDNF (Val66Met) with the risk of PD and suggest a synergic effect of rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) polymorphisms on the occurrence of MLIC.