Genotyping for seven GABRA2 single nucleotide polymorphisms (SNPs), identified from the literature as positively associated with alcohol dependence, was performed with success rates of 90% or greater.
In this study, we stratified subjects who had participated in an fMRI study of alcohol cue responses according to their genotype at a SNP in GABRA2 (rs279871) shown to be associated with alcohol dependence (Edenberg et al., 2004).
First, we tested whether a single nucleotide polymorphism within GABRA2 gene, which encodes a subunit of the GABA(A) receptor, and that has been associated with AD, influences 'extreme' alcohol intake and second, the efficacy of three psychotherapies for alcoholism in treating extreme drinking behavior.
No evidence of an association was found at the allele, genotype, haplotype, or diplotype levels between the 3'-GABRA2 polymorphisms investigated and alcoholism in 149 Italian alcoholics (98 alcohol dependents and 51 alcohol abusers) and 278 controls.
The genes encoding several GABA-A receptor subunits, including GABRA2, have been associated with alcoholism, suggesting that variations in gaba signaling contribute to risk.
We conclude that genetic variation at or near the GABRA2 locus significantly affects vulnerability not only to AD, but to other forms of substance use including ND and CD, and that the effects may be sex dependent.
We describe analyses aimed at characterizing the pathway of risk associated with GABRA2, a gene previously associated with adult alcohol dependence, in a community sample of children followed longitudinally from childhood through young adulthood.
The GABRA2 locus has been found to be associated with alcohol dependence in several studies, but no functional variant that can account for this association has been identified.
These results demonstrated that GABRA2--originally associated with a diagnosis of alcohol dependence in adults--also predicted the onset of symptoms among subjects in their 20s, confirmed specific hypotheses about three other predictors in the fi nal model, and suggested the utility of incorporating biological and nonbiological predictors to optimally predict young adult alcohol problems.
In summary, these results extend previous findings and provide new insights into the putative biobehavioral mechanisms that may moderate the association between the GABRA2 gene, sensitivity to the acute effects of alcohol and ultimately alcohol dependence.
Logistic regression analysis indicated that genetic elements in the GABRG1 haplotype block likely contribute to AD risk in an additive manner, whereas those in the GABRA2 haplotype block may act in a dominant manner in relation to risk of AD.
The GABRA2 allelic associations found in clinical case-control studies have detectable but minor effects on DSM-defined alcohol dependence in the general community.
Previous studies demonstrated, and replicated, an association between single nucleotide polymorphisms (SNPs) within the GABRA2 gene and risk for alcohol dependence.
In this paper we summarize published results from linkage and association analyses of two chromosomal regions in which the use of endophenotypes has successfully led to the identification of genes associated with alcohol dependence [GABRA2 (Edenberg et al., (2004).Am.J. Hum.Genet.
Although our study was limited by the number of cases being larger than the number of controls, the results confirm GABRA2 as a susceptibility gene for alcohol dependence in the German population.