Oct. 25, 2007 While both environmental and genetic factors contribute to the risk of developing alcohol dependence, it is believed to be a largely heritable -- 52 to 64 percent -- disease. Previous research had found a significant association between risk for alcoholism and DNA sequence variations called single nucleotide polymorphisms (SNPs) within the GABRA2 gene. New findings indicate that the GABRA2 genotype can modify overall drinking behavior, and may also have an impact on the success of certain types of alcohol psychotherapy.
"The Collaborative Study on the Genetics of Alcoholism (COGA) first reported an association between alcoholism and GABRA2, based on fine mapping of the region ... by a genomic scan and linkage analysis," explained Henry R. Kranzler, professor of psychiatry at the University of Connecticut Health Center and corresponding author for the study. "We later showed that a high-risk GABRA2 allele was associated with a blunted subjective response to alcohol among healthy subjects in a human laboratory study. We considered that this allele might predict drinking behavior in alcoholics in treatment, so we designed a study to identify patient predictors of treatment response to specific psychotherapies that were clearly differentiated."
"This was an important research step because one of the main goals of work on the human genome is that genetic information will someday be used to match individuals with the treatments that are most likely to work for them," said Kent Hutchison, a professor at the University of New Mexico and director of the Neurogenetics Core at the MIND Institute. "This is one step toward realizing that potential."
Kranzler and his colleagues used data collected through Project MATCH, a multi-center randomized clinical trial evaluating the efficacy of three types of psychosocial treatment for alcoholism: Cognitive Behavioral Therapy (CBT), Motivational Enhancement Therapy (MET), and Twelve Step Facilitation (TSF). The researchers collected DNA samples from 812 European-American subjects (596 men, 216 women), and followed their passage through 12 weeks of treatment and a 12-month post-treatment period.
Results indicate that the GABRA2 genotype can modify overall alcohol intake.
"The allele in the SNP in GABRA2 that was associated by our prior research to alcohol dependence and a blunted subjective response to alcohol among social drinkers predicted drinking behavior over a 15-month period in patients being treated with psychotherapy for alcohol dependence," said Kranzler. More specifically, patients with two low-risk GABRA2 alleles had fewer drinking days and heavy-drinking days than those with one or more high-risk GABRA2 alleles.
The GABRA2 genotype may also have an impact on the success of the treatments.
"Although not hypothesized, there was also a differential response to psychotherapy based on GABRA2 genotype," said Kranzler. "Those with the low-risk genotype show greater benefit with one psychotherapy, TSF, than the other psychotherapies."
Collectively speaking, he added, these findings mean that certain genotypes may not only help to predict who might be at greatest risk of developing alcohol-related problems, but may also help to indicate which psychotherapies might have the best chance for success.
"It may be too soon to know exactly how these findings may be used in the clinic as there is much work to be done," said Hutchison. "But certainly, this is a first step in the right direction and at some point there is likely to be implications for how we match patients to specific treatments. The technology currently exists to genotype individuals on one million SNPs. At some point, we will have a panel of SNPs that can be used to match individuals with specific treatments."
Results are published in the November issue of Alcoholism: Clinical & Experimental Research. Co-authors of the paper, "Variations in GABRA2 Predicts Drinking Behavior in Project MATCH Subjects," were: Lance O. Bauer and Jonathan Covault of the Department of Psychiatry in the Alcohol Research Center at the University of Connecticut School of Medicine; Ofer Harel and Sourish Das of the Department of Statistics at the University of Connecticut; Joel Gelernter of the Department of Psychiatry in the Division of Human Genetics in Psychiatry at Yale University School of Medicine; and Raymond Anton of the Department of Psychiatry and Behavioral Sciences at the Medical University of South Carolina. The study was funded by the National Institutes of Health.
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