Variation in GABRA2 predicts drinking behavior in project MATCH subjects

Abstract

Background: Previous studies demonstrated, and replicated, an association between single nucleotide polymorphisms (SNPs) within the GABRA2 gene and risk for alcohol dependence. The present study examines the association of a GABRA2 SNP with another definition of alcohol involvement and with the effects of psychosocial treatment.

Methods: European-American subjects (n = 812, 73.4% male) provided DNA samples for the analysis. All were participants in Project Matching Alcoholism Treatment to Client Heterogeneity (MATCH), a multi-center randomized clinical trial evaluating the efficacy of 3 types of psychosocial treatment for alcoholism: Cognitive Behavioral Therapy (CBT), Motivational Enhancement Therapy (MET), or twelve-step facilitation (TSF). The daily probabilities of drinking and heavy drinking were estimated during the 12-week treatment and 12-month post-treatment periods.

Results: Subjects homozygous for the allele associated with low risk for alcohol dependence in previous studies had lower daily probabilities of drinking and heavy drinking in the present study. This low-risk allele was also associated with a greater difference in drinking outcomes between the treatments. In addition, it enhanced the relative superiority of TSF over CBT and MET. Population stratification was excluded as a confound using ancestry informative marker analysis.

Conclusions: The assessment of genetic vulnerability may be relevant to studies of the efficacy of psychosocial treatment: GABRA2 genotype modifies the variance in drinking and can therefore moderate power for resolving differences between treatments.

Figure 1

Daily probability of drinking during and after the 12-week treatment period as a function of genotype (high-risk = A/G or G/G; low-risk = A/A) and treatment assignment (CBT = Cognitive-Behavioral Treatment, MET = Motivational Enhancement Therapy, TSF = Twelve-Step Facilitation).

Figure 2

Daily probability of heavy drinking (men: > 5; women: > 4) during and after treatment as a function of genotype (high-risk = A/G or G/G; low-risk = A/A) and treatment assignment (CBT = Cognitive-Behavioral Treatment, MET = Motivational Enhancement Therapy, TSF = Twelve-Step Facilitation).