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.


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

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*
  • White People / genetics*


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