Elias Zintzaras1. 1. Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece. zintza@med.uth.gr
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 I2 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, I2=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, I2=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.
OBJECTIVES: The available published evidence from the genetic association studies on the association between alcoholism and catechol-O-methyl transferase472G/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 I2 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, I2=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, I2=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 transferase472G/A is a marker associated with alcoholism. More evidence is needed to draw safe conclusions regarding this association.