GABA Receptors Genes Polymorphisms and Alcohol Dependence: No Evidence of an Association in an Italian Male Population
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Objective: The genes encoding for gamma-aminobutyric acid (GABA) A and B receptors may be considered as candidatesfor alcoholism; genetic alterations at this level may produce structural and functional diversity and thus play a role in the responseto alcohol addiction treatment. To investigate these aspects further, we conducted a preliminary genetic association study ona population of Italian male alcohol addicts, focusing on GABA A and B receptors. Methods: A total of 186 alcohol-dependent subjects (in the first phase 139, then 47 more samples) and 182 controls were genotypedfor 25 single nucleotide polymorphisms (SNPs) of genes encoding the alpha-1 subunit of GABA A receptor (GABRA1) andsubunits 1 and 2 of GABA B receptor (GABBR1 and GABBR2). The chi-squared test for allele and genotype distributions andHardy-Weinberg equilibrium analysis of both subjects and controls were performed. Bonferroni’s correction for multiple comparisonswas applied. Results: Preliminary results comparing 139 alcohol-dependent subjects and 182 controls showed differences in genotype distributionin the former for SNP rs29253, located in the intron region of the GABBR1 gene. In order to clarify the meaning ofthis association, 47 more samples from alcohol-dependent subjects were tested for this SNP only: the previously found associationwas not confirmed. Conclusion: The lack of significant differences between the two groups does not provide evidence that GABRA 1 and GABBR1and 2 genes are candidates for alcoholism in this population. Further studies with larger samples are needed, together with investigation of other components of the GABA pathway.
Abstract
Objective: The genes encoding for gamma-aminobutyric acid (GABA) A and B receptors may be considered as candidatesfor alcoholism; genetic alterations at this level may produce structural and functional diversity and thus play a role in the responseto alcohol addiction treatment. To investigate these aspects further, we conducted a preliminary genetic association study ona population of Italian male alcohol addicts, focusing on GABA A and B receptors. Methods: A total of 186 alcohol-dependent subjects (in the first phase 139, then 47 more samples) and 182 controls were genotypedfor 25 single nucleotide polymorphisms (SNPs) of genes encoding the alpha-1 subunit of GABA A receptor (GABRA1) andsubunits 1 and 2 of GABA B receptor (GABBR1 and GABBR2). The chi-squared test for allele and genotype distributions andHardy-Weinberg equilibrium analysis of both subjects and controls were performed. Bonferroni’s correction for multiple comparisonswas applied. Results: Preliminary results comparing 139 alcohol-dependent subjects and 182 controls showed differences in genotype distributionin the former for SNP rs29253, located in the intron region of the GABBR1 gene. In order to clarify the meaning ofthis association, 47 more samples from alcohol-dependent subjects were tested for this SNP only: the previously found associationwas not confirmed. Conclusion: The lack of significant differences between the two groups does not provide evidence that GABRA 1 and GABBR1and 2 genes are candidates for alcoholism in this population. Further studies with larger samples are needed, together with investigation of other components of the GABA pathway.
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