The GABRA2 Gene and Subtypes of Alcohol Dependence

Studies have shown an association between the gene that codes for a subunit of the gamma-aminobutryic acid type A receptor (GABRA2) and alcohol dependence. To determine whether variations in the GABRA2 gene are associated with subtypes of alcohol dependence, researchers in Germany genotyped 257 inpatients with dependence and 88 healthy controls. The examined subtypes were a positive family history (1 or more first-degree relatives with alcohol dependence), a negative family history, early onset (<26 years old at diagnosis), late onset, alcohol withdrawal seizures, delirium tremens, and anti-social personality disorder.

• A specific GABRA2 haplotype was significantly more common in patients with dependence than in controls (45% versus 29%, respectively; odds ratio [OR] 2.0).
• This “higher-risk” haplotype was also significantly associated with most subtypes of alcohol dependence (ORs ranging from approximately 1.9 to 2.6 compared with controls) and was most likely in patients with a positive family history.

Comments:

This study supports prior data indicating that a GABRA2 haplotype may increase susceptibility for alcohol dependence. Although the higher-risk GABRA2 haplotype was most common in patients with a presumed “higher genetic load” (those with a positive family history of dependence), its prevalence was similar across the subtypes. The clinical utility of uncovering susceptibility genes such as GABRA2 is uncertain.

Kevin L. Kraemer, MD, MSc

Reference:

Fehr C, Sander T, Tadic A, et al. Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis. Psychiatr Genet. 2006;16(1):9–17.