|Scientists Identify Gene That Influences Alcohol
A variant of a gene involved in communication among brain cells
has a direct influence on alcohol consumption in mice, according
to a new study by scientists supported by the National Institute
on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes
of Health (NIH), and the U.S. Army.
Scientists do not know yet whether a similar gene variant, with
a similar effect on alcohol consumption, exists in humans.
Known as Grm7, the gene encodes a receptor subtype that inhibits
the release of glutamate and other neurotransmitter molecules that
brain cells use to communicate with one another. Researchers identified
a gene variant, or polymorphism, that reduces the abundance of
Grm7 messenger RNA (mRNA) in brain tissue. mRNA is the molecular
intermediate between a gene and its protein product. Mice that
possess this gene variant drink more alcohol than do mice with
higher brain levels of Grm7 mRNA. A report of the study appears
in the December, 2007 issue of Genomics.
"This is a noteworthy contribution, particularly since identifying
genes that predispose to alcohol-related behaviors is such an arduous
task," says NIAAA Director Ting-Kai Li, M.D.
Scientists have long known that genes account for a significant
proportion of the risk for alcoholism. However, the fact that there
are multiple such genes that interact with each other and with
multiple environmental factors to influence drinking behavior has
hampered studies aimed at isolating individual genes.
"Controlling for this background noise — the various
gene-gene and gene-environment interactions — presents considerable
methodological challenges," notes first author Csaba Vadasz,
Ph.D., professor of psychiatric research in the department of psychiatry
at New York University School of Medicine, and Director of the
NeuroBehavioral Genetic Research Program at the Nathan Kline Institute
in Orangeburg, N.Y.
To overcome these difficulties, Dr. Vadasz and colleagues applied
a variety of genetic and analytic techniques to animals having
nearly identical genetic background, but differing in their preference
for alcohol, to identify a chromosomal region, and ultimately the
Grm7 gene, associated with alcohol preference.
"Our findings support emerging evidence of the critical role
that the brainís glutamate pathways play in addiction," says
Dr. Vadasz. "While dopamine has traditionally been cast as
a central actor in the neurochemistry of substance use and abuse,
recent studies indicate that glutamate systems play an important
role in reinforcement and addiction."
If further studies show that a similar gene variant is relevant
to alcohol problems in humans, the finding by Dr. Vadasz and colleagues
may lead to new opportunities for developing drugs to treat alcohol
dependence. Dr. Vadasz speculates that such drugs might be designed
to control the level of the Grm7 gene product or modulate the activity
of the gene product itself.
The National Institute on Alcohol Abuse and Alcoholism, part of
the National Institutes of Health, is the primary U.S. agency for
conducting and supporting research on the causes, consequences,
prevention, and treatment of alcohol abuse, alcoholism, and alcohol
problems and disseminates research findings to general, professional,
and academic audiences. Additional alcohol research information
and publications are available at www.niaaa.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.