Meta-analysis of the COMT Val158Met polymorphism in major depressive disorder: the role of gender

OBJECTIVES: 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.