Relationship of MAO-A promoter (u-VNTR) and COMT (V158M) gene polymorphisms to CSF monoamine metabolites levels in a psychiatric sample of caucasians: A preliminary report

Am J Med Genet B Neuropsychiatr Genet. 2005 Jan 5;132B(1):100-3. doi: 10.1002/ajmg.b.30094.

Abstract

Monoamine oxidase A gene promoter (MAOA-uVNTR) and catechol-O-methyltransferase V158M (COMT-V158M) gene functional polymorphisms are reported to be associated with impulsive-aggression, but a biological intermediate effect remains to be determined. This study assessed the association of these polymorphisms with cerebrospinal fluid (CSF) monoamine metabolites as endophenotypes. Ninety-eight Caucasian psychiatric subjects were assessed for Axis I and II diagnosis. Subjects were genotyped for the functional polymorphisms, MAOA-uVNTR and COMT-V158M. CSF was obtained by lumbar puncture. Relationships of the two polymorphism to monoamine metabolites: HVA, 5-HIAA, and MHPG were examined. The higher-expressing MAOA-uVNTR genotype was associated with higher CSF-HVA levels in males only (n = 46) (195.80 pmol/ml, SD = 61.64 vs. 161.13, SD = 50.23, respectively; P = 0.042). No association was found with diagnosis. COMT-V158M had no association with CSF monoamine metabolites. The association of MAOA-uVNTR with dopaminergic activity in males is a preliminary finding that needs to be replicated in a larger sample of Caucasian males and relationships sought with clinical phenotypes. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Substitution / genetics
  • Catechol O-Methyltransferase / genetics*
  • Female
  • Genotype
  • Homovanillic Acid / cerebrospinal fluid
  • Humans
  • Hydroxyindoleacetic Acid / cerebrospinal fluid
  • Linkage Disequilibrium
  • Male
  • Mental Disorders / cerebrospinal fluid
  • Mental Disorders / genetics*
  • Methoxyhydroxyphenylglycol / cerebrospinal fluid
  • Middle Aged
  • Minisatellite Repeats / genetics
  • Monoamine Oxidase / cerebrospinal fluid
  • Monoamine Oxidase / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics*
  • Whites / genetics*

Substances

  • Methoxyhydroxyphenylglycol
  • Hydroxyindoleacetic Acid
  • Monoamine Oxidase
  • Catechol O-Methyltransferase
  • Homovanillic Acid