"These findings help demonstrate that regardless what different environmental factors in Russia may be at play, the genetic variations still seem to be influencing risk in that population," said Jaako Lappalainen, M.D., assistant professor of psychiatry in the Center for the Translational Neuroscience of Alcoholism at Yale, and first author of the study.
The variations are in a subtype of gamma-amino butyric acid (GABA) receptor, which is the most abundant inhibitory neurotransmitter in the brain. Two large genetic studies in the U.S. last year identified an association between genetic variations in the GABRA2 receptor subtype and risk for alcohol dependence, Lappalainen said.
"There are braking neurotransmitters and accelerating neurotransmitters," he said. "GABA is one of the braking neurotransmitters. It puts the brakes on neurons so that they don't get out of control. Activating the function of GABA receptors usually decreases activity in brain neurons and can decrease activity of the entire brain and body, as occurs in general anesthesia. Some of alcohol's effects appear to be mediated through GABRA2."
This gene is often found in persons who do not become alcoholic, but its presence causes a small increase in risk that appears to be consistent across U.S. and Russian populations, Lappalainen said. It is not known how the mechanism increases the risk.
For this study, researchers recruited and drew blood samples from 113 Russian alcohol-dependent men at a St. Petersburg treatment center and100 local military personnel as controls. Each sample was genotyped for seven GABRA2 single nucleotide polymorphisms (SNPs), which are variations between individuals in the genetic code. Lappalainen and his colleagues found significant associations between two SNPs and alcohol dependence. The structure and frequencies of the variations were similar in both U.S. and Russian populations.
Lappalainen stressed that other genes have been implicated in alcoholism and that the risk of alcohol dependence is also dependent on environment and behavior.
The study was funded by the National Institutes of Health, the Alcoholic Beverage Medical Research Foundation, the U.S. Department of Veterans Affairs, and the Ethel F. Donaghue Women's Health Investigator Program at Yale.
Alcoholism: Clinical & Experimental Research 29: 493-498 (April 2005)
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