MAO-B and COMT Genetic Variations Associated With Levodopa Treatment Response in Patients With Parkinson's Disease.

Abstract

The most commonly used Parkinson's disease (PD) treatment is the replacement of dopamine by its levodopa precursor (l-dopa). Monoamine oxidase-B (MAO-B) and catechol-o-methyl transferase (COMT) are enzymes involved in the metabolism and regulation of dopamine availability. In our study we investigated the possible relation among selected single-nucleotide polymorphisms (SNPs) in the MAO-B (rs1799836) and COMT (rs4680) genes and the therapeutic response to levodopa (l-dopa). A total of 162 Brazilian patients from the Pro-Parkinson service of Clinics Hospital of Pernambuco diagnosed with sporadic PD and treated with levodopa were enrolled. PD patients were stratified into 2 groups according to the daily levodopa dose. MAO-B and COMT SNP genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism. After multivariate analysis, we observed a significant difference between PD groups for the following variables: sex (P = .02), longer duration of disease (P = .02), longer levodopa therapy duration (P = .01), younger onset of PD (P = .01), and use of COMT inhibitor (P = .02). We observed that patients carrying MAO-B (rs1799836) A and AA genotypes and COMT (rs4680) LL genotype suffered more frequently from levodopa-induced-dyskinesia. In addition, we found an increased risk of 2.84-fold for male individuals carrying the MAO-B G allele to be treated with higher doses of levodopa (P = .04). We concluded that before beginning PD pharmacological treatment, it is important to consider the genetic variants of the MAO-B and COMT genes and the sex, reinforcing the evidence that sexual dimorphism in the genes related to dopamine metabolism might affect PD treatment.

• Authors: Tiago Furtado Sampaio, Erinaldo Ubirajara Damasceno Dos Santos, Gessica Dayane Cordeiro de Lima, Rute Salgues Gueiros Dos Anjos, Ronaldo Celerino da Silva, Amdore Guescel C Asano, Nadja Maria Jorge Asano, Sergio Crovella, Paulo Roberto Eleutério de Souza
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 58 Issue 7 Pg. 920-926 (07 2018) ISSN: 1552-4604 [Electronic] England
• PMID: 29578580 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018, The American College of Clinical Pharmacology.

Chemical References

• Antiparkinson Agents
• Levodopa
• Monoamine Oxidase
• COMT protein, human
• Catechol O-Methyltransferase
• Dopamine

Topics

• Adult
• Aged
• Antiparkinson Agents (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Biological Availability
• Brazil
• Catechol O-Methyltransferase (genetics)
• Dopamine (metabolism)
• Dose-Response Relationship, Drug
• Dyskinesias
• Female
• Genotype
• Humans
• Levodopa (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Male
• Middle Aged
• Monoamine Oxidase (genetics)
• Parkinson Disease (drug therapy, enzymology, genetics)
• Pharmacogenomic Variants (drug effects)
• Polymorphism, Single Nucleotide
• Retrospective Studies
• Sex Characteristics
• Surveys and Questionnaires