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See Inside April 2007

Seeking the Connections: Alcoholism and Our Genes

Identifying genetic influences on vulnerability to alcohol addiction can lead to more targeted treatments and help those at risk to make informed choices about their own lives
Alcohol



IAN MCKINNELL Photonica/Getty Images (man with glass); BRIAN BERMAN Taxi/Getty Images (baby face); EMILY HARRISON (photoillustration)

The tendency to become dependent on alcohol has long been known to run in families, which for some only added to the social stigma attached to this complicated condition. But to scientists, that apparent heritability suggested that some genetic component underlying vulnerability to alcohol problems was being transmitted from generation to generation.

With rapid advances over the past 10 years in technologies for discovering and analyzing the functions of genes, researchers are now increasingly able to get at the biological roots of complex disorders such as substance abuse and addiction. The power to examine patterns of inheritance in large populations, and to survey hundreds of thousands of tiny variations in the genomes of each of those individuals, enables investigators to pinpoint specific genes that exert strong or subtle influences on a person's physiology and his or her resulting risk for disease.

As is true of many other human disorders, alcoholism does not have a single cause, nor is its origin entirely genetic. Genes can play an important role, however, by affecting processes in the body and brain that interact with one another and with an individual's life experiences to produce protection or susceptibility. Teasing these effects apart is challenging, and to date fewer than a dozen genes that influence one's risk for alcoholism have been identified, although more surely exist.

Variants of each of the known genes only modestly alter an individual's vulnerability to alcohol, but many are common in the general population and may have wider effects on drinking habits, on other addictions or problematic behaviors, and on disorders such as depression and anxiety. Finding the genes involved in our responses to alcohol and understanding their effects may thus illuminate a broader array of conditions, too. Revealing the biological processes that can build and reinforce alcohol addiction will most certainly help to better target existing treatments and devise new ones to break alcohol's hold.

Clues in Human Variations
Genes powerfully influence a person's physiology by giving rise to some 100,000 different types of protein, each of which has a direct role in the daily functioning of the body and brain or in regulating the activity of other genes. The strong connection between variations in basic physiology and an individual's susceptibility to alcohol problems is well illustrated by the very first gene to be identified as affecting the risk of developing alcohol dependence.

Decades ago researchers began investigating the widely observed tendency of persons from Chinese, Japanese or other East Asian backgrounds to become "flushed" when they drank an alcoholic beverage. Blood tests on subjects displaying this effect showed increased levels of acetaldehyde, a breakdown product of alcohol, which resulted in an uncomfortable sensation of warmth in the skin, palpitations and weakness. By the 1980s investigators traced the reaction to an enzyme involved in alcohol metabolism, aldehyde dehydrogenase, and eventually to the gene that encodes it, ALDH1. The enzyme breaks down acetaldehyde, but slight variations in the gene's DNA code in these subjects caused the enzyme to work more slowly. When these individuals ingested alcohol, the acetaldehyde--which may be toxic in high doses--was building up in their bodies.

This ALDH1 gene variant has since been found to be common in Asian populations--seen in 44 percent of Japanese, 53 percent of Vietnamese, 27 percent of Koreans and 30 percent of Chinese (including 45 percent of Han Chinese)--yet it is rare in people of European descent. As might be expected, people with this slow-metabolizing gene variant also have a decreased risk, by up to sixfold, for alcoholism, so it is an example of a genetic variation that can protect against developing the disorder.

 


People who meet criteria for dependence often have multiple cases of alcoholism in their families.

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