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

Authors

  • Gil Zalsman,

    Corresponding author
    1. Department of Neuroscience, New York State Psychiatric Institute, and the Department of Psychiatry, Columbia University, New York, New York
    2. Geha Mental Health Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    • Department of Neuroscience, New York State Psychiatric Institute, Columbia University, 1051 Riverside Drive, Box 42, New York, NY 10032.
    Search for more papers by this author
  • Yung-yu Huang,

    1. Department of Neuroscience, New York State Psychiatric Institute, and the Department of Psychiatry, Columbia University, New York, New York
    Search for more papers by this author
  • Jill M. Harkavy-Friedman,

    1. Department of Neuroscience, New York State Psychiatric Institute, and the Department of Psychiatry, Columbia University, New York, New York
    Search for more papers by this author
  • Maria A. Oquendo,

    1. Department of Neuroscience, New York State Psychiatric Institute, and the Department of Psychiatry, Columbia University, New York, New York
    Search for more papers by this author
  • Steven P. Ellis,

    1. Department of Neuroscience, New York State Psychiatric Institute, and the Department of Psychiatry, Columbia University, New York, New York
    Search for more papers by this author
  • J. John Mann

    1. Department of Neuroscience, New York State Psychiatric Institute, and the Department of Psychiatry, Columbia University, New York, New York
    Search for more papers by this author

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. © 2004 Wiley-Liss, Inc.

Ancillary