Alcohol use disorder and GABAB receptor gene polymorphisms in an Italian sample: haplotype frequencies, linkage disequilibrium and association studies

Background: Alcohol use disorder (AUD) is a complex trait with genetic and environmental influences. Several gene variants have been associated with the risk for AUD, including genes encoding the sub-units of the γ-aminobutyric acid (GABA) receptors. Aim: This study evaluated whether specific single nucleotide polymorphisms (SNPs) in genes encoding GABAB receptor sub-units can be considered as candidates for the risk of AUD. Subjects and methods: Seventy-four AUD subjects and 128 Italian controls were genotyped for 10 SNPs in genes encoding GABA-B1 and GABA-B2 sub-units (GABBR1 and GABBR2). Allele, genotype, and haplotype frequencies were tested for the association with the AUD trait. Results: A significant difference between AUD individuals and controls was observed at genotype level for rs2900512 of GABBR2 gene. The homozygous T/T genotype was not found in the controls, whereas it was over-represented in the AUD individuals. Under the recessive model (T/T vs C/T + C/C) this result was statistically significant, as well as the Odds Ratio for the association with the AUD trait. Conclusions: The results provide preliminary data on the association between GABAB receptor gene variation and risk of AUD. To confirm this finding, studies with larger samples and additional characterisation of the phenotypic AUD trait are required.