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

Zintzaras, Eliasa,b

doi: 10.1097/YPG.0b013e3283413615
Original Articles

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 (ORG), 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 ORG was also nonsignificant (ORG=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.

aDepartment of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece

bInstitute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University, School of Medicine, Boston, Massachusetts, USA

Correspondence to Elias Zintzaras, PhD, Department of Biomathematics, University of Thessaly School of Medicine, 2 Panepistimiou Street, Larissa 41110, Greece Tel/fax: +30 2410 565063; e-mail:

Received March 7, 2010

Accepted June 20, 2010

© 2011 Lippincott Williams & Wilkins, Inc.