title: Meta-analysis of the COMT Val158Met polymorphism in major depressive disorder: the role of gender.
abstract: OBJECTIVE
  Many studies have reported an association of the COMT Val158Met polymorphism and major depressive disorder (MDD), although with conflicting results. The role of gender is a possible modulator. To overcome the problem of poor sample size detecting genes of small effect, we perform a meta-analysis of the current literature, investigating the influence of the COMT Val158Met polymorphism on the pathogenesis of MDD, with a major focus on the effect of gender.
  
  
  METHODS
  Out of 977 retrieved articles, 21 included case-control studies allowed the analysis of 9005 patients with MDD and 12,095 controls. Allelic and genotypic pooled odds ratios (OR) were calculated for the total sample and gender-subgroups.
  
  
  RESULTS
  In the absence of publication bias, allelic and genotypic analyses showed no significant association in the total sample, as well as in gender-specific subgroups. Sensitivity analysis did not alter the ORs.
  
  
  CONCLUSIONS
  The results imply a complex nature of the genotype × phenotype interaction. Further studies of the COMT gene or the locus remain to be justified given the important positional and functional relevance and the plethora of gender-specific findings. A possible way to further dissect this topic is shifting the focus to gene-based or genome-wide analyses of intermediate phenotypes.
authors.affiliation: a Department of Psychiatry and Psychotherapy , Medical University of Vienna , Vienna , Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Klein
authors.affiliation: b Department of Neurology , Medical University of Vienna , Vienna , Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schmoeger
authors.affiliation: a Department of Psychiatry and Psychotherapy , Medical University of Vienna , Vienna , Austria.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.affiliation: a Department of Psychiatry and Psychotherapy , Medical University of Vienna , Vienna , Austria.|c Zentrum Für Seelische Gesundheit Leopoldau , Vienna , Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schosser
mesh_terms: D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: COMT; Meta-analysis; Val158Met; gender; major depressive disorder