GABA receptor mutation linked to alcoholism risk

kofi kofi at anon.un
Tue Apr 20 20:09:30 EST 2004


   Indiana University

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Alcoholism Risk Linked To Gene Involved In Brain Chemistry

Indianapolis -- A research team headed by Indiana University School of 
Medicine scientists has identified a gene that is strongly linked to an 
individual's risk of developing alcoholism.

The gene identified, GABRA2, is one of several genes that produce parts 
of the receptor for the brain's primary inhibitory neurotransmitter, 
GABA. GABA is a chemical messenger that carries information between 
nerve cells; when GABA binds to the GABA-receptors on a nerve cell, it 
inhibits the firing of that cell. GABA is known to be involved with some 
of the body's responses to alcohol consumption, such as loss of physical 
coordination, effect on mood, and alcohol withdrawal symptoms. 

Alcoholism, which affects nearly 14 million Americans and can cause many 
social and health problems costing society an estimated $185 billion 
annually, is what scientists call a "complex" disease, meaning that many 
genes as well as environmental factors play a role in whether a person 
develops the disease. 

While there is not one single "gene that causes alcoholism" the 
statistical link between this gene and the risk for alcoholism is 
powerful, said Howard J. Edenberg, Ph.D., Chancellor's Professor at the 
IU School of Medicine. Edenberg was the lead researcher for the study, 
which appears in the April issue of the American Journal of Human 

"Statistically, this is very strong evidence that this gene affects the 
risk of alcoholism," said Edenberg, professor of biochemistry and 
molecular biology and of medical and molecular genetics.

As researchers identify genes and brain signaling pathways associated 
with alcoholism -- and learn how they vary from one person to another -- 
opportunities should arise for development of more precisely targeted 
drugs, and for individualized approaches to prevent and treat 
alcoholism, Edenberg said.

"We may be able to target therapies and preventative treatments based on 
individual characteristics," he said. The research was done as part of 
the Collaborative Study on the Genetics of Alcoholism, a 15-year-old 
project that involves scientists at nine institutions across the country 
and is funded by the National Institute on Alcohol Abuse and Alcoholism, 
part of the National Institutes of Health.

The research team's analysis involved 2282 individuals from 262 families 
selected for study because they contained at least three alcoholic 
members. Earlier genetic analyses by this team implicated a particular 
section of chromosome 4 as affecting both the risk for alcoholism and 
certain types of brainwave patterns that have been linked to alcoholics. 
Within that region are genes that make proteins enabling GABA to signal 
to nerve cells and so do its work in the brain.

The researchers analyzed tiny differences in the sequences of the genes 
and determined that differences in just one of the GABA-receptor genes, 
GABRA2, were associated with alcoholism. The same gene was associated 
with the brainwave patterns.


Edenberg is director of the Center for Medical Genomics at IU, where the 
genotyping for this study was performed. The Center's resources were 
funded in large part by the Indiana Genomics Initiative, as well as the 
state of Indiana's 21st Century Research and Technology Fund.


This story has been adapted from a news release issued by Indiana 


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