Genes and Alcohol

Dec 16, 2007
Scientists Identify Gene That Influences Alcohol
Consumption

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 brain’s 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.

Source: NIH