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Genes can trigger or protect against alcohol dependency

By Judy Foreman, Globe Columnist | October 19, 2004  

In the old days, people used to debate whether alcoholism was a disease or a moral failing. Now it is abundantly clear that not only is it a disease but one with a strong genetic component.

At least 50 percent of the vulnerability to alcoholism is now believed to be triggered by genetics, and the other 50 percent by environment, such as living in a culture where heavy drinking is endemic.


What's also increasingly clear is that many genes play a role and that genes work both ways -- with some protecting people against alcoholism and others greatly raising the risk, said Dr. Mary-Anne Enoch, a research physician at the National Institute of Alcohol Abuse and Alcoholism.

Certain groups of people, for instance, like many Japanese, Chinese and Jews, carry genes that protect against alcoholism by raising levels of particular liver enzymes so that it's unpleasant to keep drinking because of nausea, flushing and rapid heart beat.


Others, including many Caucasians, carry genes that act in the brain rather than the liver and raise the risk of becoming an alcoholic, although if people with these genes never touch a drop, they will never become alcoholics. Overall, those with a parent or sibling who is alcoholic are at three to four times the normal risk.


Even with no genetic predisposition, people can become alcoholics by constant exposure to alcohol, which turns on genes in brain cells ''that set up a vicious cycle of wanting or needing more and more alcohol," said Bill Carlezon, director of the Behavioral Genetics Laboratory at McLean Hospital.


The goal of this genetics research is to better understand alcoholism in order to design better drugs to protect people from it.


The latest statistics, released in August by the government, show that alcohol problems are on the rise. An estimated 17.6 million American adults -- 8.5 percent of the population -- now fit the diagnostic criteria for having an alcohol-use disorder. Alcohol abuse is often defined as recurrent drinking that disrupts work, school or home life or occurs in hazardous situations; alcohol dependence, also known as alcoholism, is defined as impaired control over drinking, preoccupation with drinking, withdrawal symptoms or high tolerance to alcohol.


For several years now, researchers have suspected that heavy drinkers drink as a form of self-medication -- to calm overactive circuits in the brain. Several months ago, researchers at Indiana University School of Medicine reported findings on a study of 1,547 families that support this theory.


The researchers, led by Howard J. Edenberg, a professor of biochemistry, molecular biology and molecular genetics, found that variations in one gene raise the risk of alcoholism. This gene acts on GABA, one of the brain's chief inhibitory neurotransmitters whose job is to slow down -- or calm -- the firing of certain brain nerves. Tranquilizing drugs like Valium and alcohol increase the ability of GABA to calm neural circuits.


People with a ''high-risk" variant of the GABA gene are at 40 percent increased risk of becoming alcohol-dependent.


According to researchers at the University of California at San Diego, another GABA gene also seems to raise the risk of alcoholism, in this case by programming people to drink more to get the same effect as others, said Dr. Marc Schuckit, a professor of psychiatry at the San Diego VA Hospital and UCSD School of Medicine. This trait is common in some Native Americans and Koreans.


On the flip side, the genetic protection against alcoholism only goes so far: It can be overridden if a person persistently drinks heavily, Dr. Deborah Hasin, a professor at Columbia University, has shown.


Hasin studied Jews with the protective gene who had grown up in Israel and those who had immigrated to Israel from Russia, where heavy drinking is common. The Russian Jews were more likely to be alcoholics, Hasin said, showing that both genetics and environment clearly play a role.


That finding also was supported by a study by Christina Barr, a research fellow at the National Institute on Alcohol Abuse and Alcoholism. She found that female monkeys who were separated from their mothers in childhood and had high-risk genes were more likely to become alcoholics than monkeys with just the gene or just the unpleasant history.


The bottom line: So far, there are no genetic tests to tell if you're predisposed to alcohol problems. But if you're worried, talk to your doctor or drop in on an Alcoholics Anonymous meeting.


Judy Foreman is a freelance columnist who can be contacted at foreman@globe.com.
┬ę Copyright 2004 Globe Newspaper Company.

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