Dataset Information

Genetic variations in catechol-O-methyltransferase gene are associated with levodopa response variability in Chinese patients with Parkinson's disease.

ABSTRACT: Catechol-O-methyltransferase (COMT) is one of the main enzymes in dopamine metabolism and is reported to be associated with susceptibility to Parkinson's disease (PD) and pharmacotherapy. However, researchers mostly focus on the most common polymorphism, rs4680. In this case-control study, we investigated the association of SNPs other than rs4680 with the levodopa (L-dopa) response and other clinical features in Chinese PD patients. Eleven single nucleotide polymorphisms (SNPs) in the COMT gene were genotyped, and clinical data were collected. Patients with the TT genotype of rs165728 or rs174699 had larger daily levodopa equivalent doses (LEDs) than the patients with CC and CT genotypes under the dominant model (p?=?0.01421 for rs165728 and p?=?0.02302 for rs174699). Under the dominant model, the patients with GG at rs4680 G?>?A had a lower occurrence of dyskinesia than those with AA and AG (p?=?0.0196). Patients with CC at rs4633 had a lower occurrence of dyskinesia than those with TT and TC (p?=?0.0429) under the dominant model. The frequencies of the rs174675 T and rs933271 C alleles were higher in PD patients than in the controls (p?

SUBMITTER: Zhao C

PROVIDER: S-EPMC7293305 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic variations in catechol-O-methyltransferase gene are associated with levodopa response variability in Chinese patients with Parkinson's disease.

Zhao Cuiping C Wang Yihua Y Zhang Bin B Yue Yaoxian Y Zhang Jianyuan J

Scientific reports 20200612 1

Catechol-O-methyltransferase (COMT) is one of the main enzymes in dopamine metabolism and is reported to be associated with susceptibility to Parkinson's disease (PD) and pharmacotherapy. However, researchers mostly focus on the most common polymorphism, rs4680. In this case-control study, we investigated the association of SNPs other than rs4680 with the levodopa (L-dopa) response and other clinical features in Chinese PD patients. Eleven single nucleotide polymorphisms (SNPs) in the COMT gene ...[more]

PMID: 32533012

Similar Datasets

Project description:BackgroundAs Parkinson's disease progresses, levodopa treatment loses efficacy, partly through the loss of the endogenous dopamine-synthesizing enzyme L-amino acid decarboxylase (AADC). In the phase I PD-1101 study, putaminal administration of VY-AADC01, an investigational adeno-associated virus serotype-2 vector for delivery of the AADC gene in patients with advanced Parkinson's disease, was well tolerated, improved motor function, and reduced antiparkinsonian medication requirements.ObjectivesThis substudy aimed to determine whether the timing and magnitude of motor response to intravenous levodopa changed in PD-1101 patients after VY-AADC01 administration.MethodsParticipants received 2-hour threshold (0.6 mg/kg/h) and suprathreshold (1.2 mg/kg/h) levodopa infusions on each of 2 days, both before and approximately 6 months after VY-AADC01. Infusion order was randomized and double blinded. Unified Parkinson's Disease Rating Scale motor scores, finger-tapping speeds, and dyskinesia rating scores were assessed every 30 minutes for 1 hour before and ≥3 hours after start of levodopa infusion.ResultsOf 15 PD-1101 patients, 13 participated in the substudy. Unified Parkinson's Disease Rating Scale motor score area under the curve responses to threshold and suprathreshold levodopa infusions increased by 168% and 67%, respectively, after VY-AADC01; finger-tapping speeds improved by 162% and 113%, and dyskinesia scores increased by 208% and 72%, respectively, after VY-AADC01. Adverse events (mild/moderate severity) were reported in 5 participants during levodopa infusions pre-VY-AADC01 and 2 participants post-VY-AADC01 administration.ConclusionsVY-AADC01 improved motor responses to intravenous levodopa given under controlled conditions. These data and findings from the parent study support further clinical development of AADC gene therapy for people with Parkinson's disease. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Dataset Information

Genetic variations in catechol-O-methyltransferase gene are associated with levodopa response variability in Chinese patients with Parkinson's disease.

Publications

Genetic variations in catechol-O-methyltransferase gene are associated with levodopa response variability in Chinese patients with Parkinson's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets