Is catechol-O-methyl transferase 472G/A gene polymorphism a marker associated with alcoholism?

Abstract

Objectives The available published evidence from the genetic association studies on the association between alcoholism and catechol-O-methyl transferase 472G/A gene polymorphism have produced inconclusive results. To interpret these results, a meta-analysis of all available studies was conducted. Methods PubMed database and HuGE Navigator were searched for all relevant genetic association studies. In the meta-analysis, the random effect pooled odds ratio (OR) was estimated. The heterogeneity between studies was tested using the Q statistic and the I(2) metric. A spectrum of genetic contrasts was examined and the existence of potential bias was investigated. Cumulative meta-analysis was also performed. In addition, the pooled generalized OR (OR(G)), which uses the complete genotype distribution, was calculated. Results Data from eight gene-candidate studies were included in the meta-analysis. The main analysis for the allele contrast derived a nonsignificant association (OR = 1.14, confidence interval: 0.95-1.36) and large heterogeneity (P(Q) = 0.03, I(2) = 56%). In subgroup analysis, the genetic effects were consistent across ethnicities, and sex, with the associations being nonsignificant. The associations according to violent behaviour status were also nonsignificant. Heterogeneity varied from low to high. A lack of differential magnitude of effect in large versus small studies was revealed. Cumulative meta-analysis indicated a trend towards association as evidence accumulates. The OR(G) was also nonsignificant (OR(G) = 1.14, confidence interval: 0.94-1.41), (P(Q) = 0.04, I(2) = 53%). The genome-wide and the family-based association studies did not produce significant associations. Conclusion There is no conclusive evidence that catechol-O-methyl transferase 472G/A is a marker associated with alcoholism. More evidence is needed to draw safe conclusions regarding this association. Psychiatr Genet 21:29-36 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.