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Chromosomal Regions Linked to Alcoholism

May Lead to the Identification of Specific Genes

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Updated July 15, 2003

A study in the July 2003 issue of Alcoholism: Clinical & Experimental Research has identified three chromosomal regions in the human genome that appear to hold genes that affect low response to alcohol.

"Prior research has shown that a significant proportion of the risk for having a low response to alcohol is genetic," said Kirk C. Wilhelmsen, principal investigator at the Ernest Gallo Clinic and Research Center and first author of the study. "In other words, most of what accounts for the variation among us in terms of our response to alcohol probably comes from genes. But the research doesn't tell us how many genes are involved, or how the genes work to cause this effect."

"All behavior, thinking and feeling are controlled by the actions of molecules in the brain," added Ivan Diamond, professor and Vice Chairman of the department of neurology at the University of California, San Francisco. "Brain molecules can be changed by experiences in our environment, diseases, drugs and genes. Genes control the proteins which regulate the molecules that carry out all of the functions in the brain. If we could identify genes that confer risk for alcoholism or allow alcoholism to develop, then we could begin to understand which molecules are behaving abnormally or which molecules are responsible for contributing to alcoholism."

Diamond said that identification of chromosomes and eventually, specific genes, is a logical step in ongoing research. "About 25 years ago, Dr. Marc Schuckit started to measure responses to alcohol in young college students," he said. "None of these young men were alcoholics when they were tested. Many years later, however, he discovered that those young men who exhibited a low response to a drink of alcohol were more likely to become alcoholics in the future.

"Therefore, it seems that a diminished response to alcohol appears to predict the development of alcoholism in some people. If you are easily intoxicated by small amounts of alcohol, it is unlikely that you will ever become an alcoholic. On the other hand, if you can 'hold your liquor' at an early age, you have a greater risk of becoming an alcoholic years later."

For the current study, researchers initially chose participants from students attending two San Diego universities: each was between 18 and 29 years of age, had an alcohol-dependent parent, a personal history of drinking but not alcohol dependence, and a full sibling with similar characteristics. Full siblings (n=139 pairs) and available parents were then genotyped for 811 satellite markers.

Subjects were given eight minutes to consume a beverage (20 percent by volume solution of 0.75 ml/kg of 95 percent alcohol for women and 0.90 ml/kg for men) from a closed container, designed to disguise the alcohol taste and the amount consumed. Measurements of body sway and both positive and negative subjective feelings were collected at baseline and then at 15 minutes, 30 minutes, and every half-hour thereafter during the three-hour testing session.

"We found there were three locations that had the largest evidence for genes that affect the level of response to alcohol," said Wilhelmsen. These were chromosomes 10, 11 and 22.

"Identification of chromosome locations for genes - that may affect someone's risk for becoming an alcoholic is important because this may lead to the identification of specific genes that determine how alcohol makes us feel, give us new insight into how the brain works, and help us understand why some people become addicted to alcohol," said Diamond.

Source: Alcoholism: Clinical & Experimental Research New Release.

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