Polymorphisms of COMT (c.649G>A), MAO-A (c.1460C>T), NET (c.1287G>A) Genes and the Level of Catecholamines, Serotonin in Patients with Parkinson's Disease

DNA Cell Biol. 2017 Jun;36(6):501-512. doi: 10.1089/dna.2016.3569. Epub 2017 Apr 18.

Abstract

The purpose of this study was to determine the concentration of plasma norepinephrine (NE), epinephrine (E), and serotonin (5-HT) in two collections, after a 30-min supine (I) and 5-min upright position (II), and polymorphisms of genes, COMT (c.649G>A), MAO-A (c.1460C>T), and NET (c.1287G>A), in patients with Parkinson's disease (PD) and other degenerative parkinsonism and controls. The study was performed in 49 PD patients, 19 parkinsonism patients, and 48 controls. The level of NE, E, and 5-HT was determined by HPLC/EC. PCR-RFLP was conducted to analyze the COMT, MAO-A, and NET polymorphisms. Genotypes of COMT, MAO-A, and NET genes occurred with different frequencies in patients with movement disorders and controls. NET AA occurred 4.8 times more frequently in patients with parkinsonism than in PD (p < 0.05). COMT AA genotype was associated with increased E levels [E (I) p < 0.01, E (II) p < 0.05] in PD compared to controls. Patients with parkinsonism with MAO-A TT genotype have a significantly higher level of 5-HT [5-HT (II), p < 0.05] compared to controls. Moreover, PD patients with NET GA genotype have the lowest level of NE (p < 0.05) compared to controls. It appears that COMT, MAO-A, and NET polymorphisms and levels of NE, E, and 5-HT are involved in pathogenesis of PD.

Keywords: COMT; MAO-A; NET; PD; biogenic amines.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Catechol O-Methyltransferase / genetics*
  • Catecholamines / blood*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Monoamine Oxidase / genetics*
  • Norepinephrine Plasma Membrane Transport Proteins / genetics*
  • Parkinson Disease / blood
  • Parkinson Disease / enzymology
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide*
  • Serotonin / blood*

Substances

  • Catecholamines
  • Norepinephrine Plasma Membrane Transport Proteins
  • SLC6A2 protein, human
  • Serotonin
  • Monoamine Oxidase
  • COMT protein, human
  • Catechol O-Methyltransferase