Contribution of dopaminergic polymorphisms to levodopa treatment response and drug concentration in Chinese patients with Parkinson’s disease

Background

Levodopa is the mainstay of treatments for Parkinson’s disease (PD), but large heterogeneity exists in patient response. Pharmacogenetic studies highlighted that genetic factors may play a relevant influence in this drug response variability.

Objective

To explore the relationship between dopaminergic polymorphisms, levodopa treatment response, and drug concentration in Chinese patients with PD.

Methods

Acute levodopa challenge test was conducted in 90 PD patients. Each patient underwent comprehensive neurological examination at baseline and after levodopa administration. Plasma levodopa concentrations were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Twelve genetic polymorphisms in genes encoding dopaminergic enzymes (TH, DDC, COMT, MAOB and DBH) were genotyped.

Results

Patients with the TH-rs6356 TT genotype showed higher ΔMDS-UPDRS-III scores compared to those with the CC + CT genotype after adjustment for the levodopa dose in the acute challenge test (P = 0.048). Furthermore, peak plasma levodopa concentration and Δplasma levodopa concentration were significantly higher in the TH-rs6356 TT group compared to the CC + CT group after adjustment (P = 0.007). Patients with the TH-rs6356 TT genotype exhibited a longer time to peak response compared to those with the CC + CT genotype (P = 0.042). However, this difference became non-significant after adjusting for levodopa dose (P = 0.066). The impact of other dopamine-related gene polymorphisms on levodopa efficacy appeared to be minimal in our study.

Conclusions

Our preliminary results from a relatively small patients’ sample, may suggest that the rs6356 polymorphism in the TH gene could act as a possible modifier of levodopa response in PD.