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Many genes play role in alcoholism

Special to The Times

In years past, people debated whether alcoholism was a disease or a moral failing. Today, it is abundantly clear that not only is it a disease, but also one with a strong genetic component.

At least 50% of the vulnerability to alcoholism is now believed to be triggered by genetics, and the other 50% 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 on Alcohol Abuse and Alcoholism.

For instance, some people -- such as many Japanese, Chinese and Jews -- carry genes that raise levels of particular liver enzymes when alcohol is consumed, leading to nausea, flushing and rapid heart beat. The unpleasant sensations help protect against alcoholism.

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Other people 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 would never become alcoholics.) Overall, those with an alcoholic parent or sibling 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 in Belmont, Mass.

Researchers of the genetics of alcoholism hope to better understand alcoholism to design more effective drugs to protect people from it.

The latest statistics, released in August by the National Institute on Alcohol Abuse and Alcoholism, show that alcohol problems are on the rise. An estimated 17.6 million American adults -- 8.5% of the population -- now fit the diagnostic criteria for having an alcohol use disorder. Definitions vary, but 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, the presence of withdrawal symptoms or a high tolerance to alcohol.

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For several years, 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 the firing of certain brain nerves. Tranquilizing drugs such as Valium and alcohol increase the ability of this neurotransmitter to calm neural circuits.

People with a “high risk” variant of the gene are at 40% increased risk of becoming alcohol dependent.

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According to researchers at UC San Diego, another GABA gene also seems to raise the risk of alcoholism, in this case by programming people to have a weak response to alcohol. These people need to drink large quantities of alcohol to get the same effect other people would get from less, said Dr. Marc Schuckit, a professor of psychiatry at the San Diego VA Hospital and UC San Diego medical school. This trait is common in some Native Americans and Koreans.

Of course, the genetic protection against alcoholism only goes so far. It can be overridden if a person persistently drinks heavily, says Dr. Deborah Hasin, a professor of clinical public health at Columbia University.

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, said Hasin, showing that genetics and environment play a role.

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

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

Some drugs may also help if your drinking is serious. Naltrexone can help reduce the craving for alcohol. Ondansetron can help reduce relapse in some alcoholics. Antabuse (disulfiram) helps by making people feel sick if they drink. And acamprosate (Campral), used in Europe but not available in the U.S., helps reduce alcohol craving.


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