Gene Discovery May Help Explain Alcoholism

Scientists find how mice metabolize booze

WEDNESDAY, May 15, 2002 (HealthDayNews) -- Did you ever wonder why some people can put down beer after beer, while others get tipsy after one glass of wine?

The difference may stem from the way the body breaks down alcohol; apparently people metabolizes alcohol differently depending on what genes they have -- or don't have.

Scientists now report that they've located some of the genes responsible for metabolizing alcohol in mice, and that the discovery should eventually lead to locating these genes in humans. The findings appear in the latest issue of the journal Alcoholism: Clinical and Experimental Research.

"We've located the position on the mouse genome of several genes that appear to affect alcohol metabolism," says the study's author, John Crabbe, the director of the Portland Alcohol Research Center and a professor at Oregon Health and Science University. "Once you know where they are on the mouse, you know 80 percent of the time where they are on the human genome."

These newly located genes affect how long it takes a mouse to sober up, according to Crabbe.

Alcohol is first converted by the body into a toxic chemical called acetaldehyde, high levels which can cause nausea, a flushed feeling, overheating and dizziness. Acetaldehyde is similar to formaldehyde, the chemical used to preserve organs for long-term storage.

In most people, acetaldehyde is quickly converted into less toxic by-products. But for some, acetaldehyde builds up in the blood and brain because they have a gene or genes that cause their bodies to process alcohol inefficiently.

In previous research, scientists learned that many people from East Asia appear to have such genes, and their bodies metabolize alcohol very slowly, according to Crabbe.

"Certain genes metabolize alcohol differently and may predispose you to avoid alcohol," explains Dr. Duane Superneau, chief of medical genetics at the Ochsner Clinic Foundation in New Orleans. "If you have these genes, you would have to be very persistent to develop the tolerance you would need to become an alcoholic. Conversely, if you're missing these genes, then you're at a higher risk for drinking more because you can tolerate it better."

Crabbe says these genes appear to be very protective in humans, making them 20 to 40 times less likely to become alcoholics.

Further research needs to be done to isolate exactly which genes cause this effect in mice, and then scientists will need to translate these findings to humans. At that point, medications or therapy could be developed to mimic the effects of these genes -- and, perhaps, insert these genes into addicts who don't have them.

"By understanding what genes a person has, you can better target treatment to the individual," Superneau says.

"The most important take-home message is that there's more evidence that alcoholism is not a single gene phenomenon," Crabbe says.

Other teams at Oregon Health and Science University, Portland Alcohol Research Center and the Portland Veterans Administration Medical Center are currently working on pinpointing the genes in mice that affect the way the body withdraws from alcohol.

What To Do

To read more about how genes affect the way alcohol is processed by the body, go to the National Institute on Alcohol Abuse and Alcoholism.

Or you can also read all about hangovers.

SOURCES: John Crabbe, Ph.D., director, Portland Alcohol Research Center, and professor of behavioral neurosciences, Oregon Health and Science University, Portland; Duane Superneau, M.D., chief, medical genetics, the Ochsner Clinic Foundation, New Orleans; May 2002 Alcoholism: Clinical and Experimental Research
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