Alcohol dependence and glutamate decarboxylase gene polymorphisms in an Italian male population

Knowledge of alcohol use disorder and of substance-related problems has recently found some initial support in genetic studies. With a view to further understanding of this particular aspect, in the light of the "self-medication hypothesis," we focused our attention on the gamma aminobutyric acid system and, in particular, on single nucleotide polymorphisms (SNPs) in the glutamate decarboxylase 67 or glutamic acid decarboxylase 67 (GAD67) gene region in association with alcohol dependence. The research was structured as a case-control study. The patient cohort included 283 Caucasian males from the Veneto region, North-east Italy; 107 were alcohol dependent according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV TR) criteria, and 176 were controls recruited from blood donors. We analyzed 26 SNPs located in the coding and untranslated regions of the GAD67 gene with the GenomeLab SNPStream Genotyping System (Beckman Coulter, Fullerton, CA). Fisher's Chi-square test for allele and genotype distributions and Hardy-Weinberg equilibrium analysis for cases and controls were performed. Ten SNPs at the GAD67 gene were valid for further statistics. Preliminary results show a difference in genotype distribution (P=.003; chi(2)=11.6081) between alcoholic subjects and controls of SNP rs 11542313 located in exon 3 of the GAD67 gene, responsible for a silent mutation (His37His). This is the first genetic study regarding the GAD67 gene in relation to the condition of alcohol dependence in an Italian population of subjects all coming from the same region (Veneto). The results highlight a statistical association between one SNP of GAD67 and the condition of alcohol dependence. To clarify the possible meaning of this association, further genetic analyses are being undertaken. In particular, we are investigating other genetic polymorphisms, both upstream and downstream from rs 11542313, which may interfere with splicing and/or GAD67 mRNA stability.