A SNP variant of rs279871, in the chromosome 4 gene encoding gamma-aminobutyric acid receptor (GABRA2), was selected due to its associations with alcoholism in young adults and with behaviors that increased risk for early drinking.
Genotyping of the 3 single nucleotide polymorphisms (SNPs) across the GABRA2 gene (rs567926, rs279858 and rs9291283) was performed in patients with alcohol dependence (N=654) and healthy control subjects (N=574).
This study examined correlates of in vitro gene expression of the AD-associated GABRA2 rs279858*C-allele in human neural cells using an induced pluripotent stem cell (iPSC) model system.
Variants in GABRA2 have been associated with adult alcohol dependence as well as phenotypic precursors, including impulsiveness and externalizing behaviors.
Although the analysis provided nominal support for an association with rs9291283 and AAD in adulthood and CD in adolescence, the current study failed to replicate previous associations between two well replicated GABRA2 SNPs and CD and alcohol dependence.
In this study, we test for genetic effects of GABRA2, a gene previously associated with alcohol dependence, on trajectories of drunkenness from age 14 to 25.
Linkage studies of alcoholism have implicated several chromosome regions, leading to the successful identification of susceptibility genes, including ADH4 and GABRA2 on chromosome 4.
We used linear mixed models to examine the effects of dutasteride and alcohol on BAES and SS responses and the interaction of dutasteride with the GABRA2alcohol dependence-associated polymorphism rs279858.
The current study examined the influence of gender, negative and positive daily life events, and GABRA2 genotype (SNP rs279871) on alcohol dependence, testing two- and three-way interactions between these variables using multi-level regression models fit to data from 2,281 White participants in the Collaborative Study on the Genetics of Alcoholism.
In addition, a gene encoding one of the receptors for the neurotransmitter γ-aminobutyric acid (GABA) known as GABRA2 seems to have a role in the development of alcohol dependence.
Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism.
Moreover, polymorphisms in the GABRA2 gene encoding the GABA(A) receptor α2 subunit have been found to be linked to chronic alcohol dependence and to polydrug abuse.
To examine these associations in greater detail, we genotyped 13 single nucleotide polymorphisms (SNPs) spanning GABRG1 and GABRA2 in 380 AAs with AD and in 253 AA controls.
Based on a haplotypic association of alcohol dependence with GABRA2, we investigated whether GABRA2 alleles are associated with the subjective responses to clamped alcohol concentration.
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.