October 20, 2010

Links Between Genetics, Alcohol Tolerance Discovered

Researchers from the University of North Carolina (UNC) School of Medicine have discovered a gene that they say plays a key role in the metabolic processing of alcohol.

The discovery of the gene CYP2E1, which was located by UNC Genetics Professor Kirk Wilhelmsen and his colleagues in the terminal region of chromosome 10, could help protect against alcoholism. Between 10% and 20% of people possess a gene variant that has been linked to a low tolerance to alcoholic beverages. As a result, they need to consume fewer glasses of beer or wine to feel inebriated.

"We have found a gene that protects against alcoholism, and on top of that, has a very strong effect," Wilhelmsen said in a statement. "But alcoholism is a very complex disease, and there are lots of complicated reasons why people drink. This may be just one of the reasons."

"It turns out that a specific version or allele of CYP2E1 makes people more sensitive to alcohol, and we are now exploring whether it is because it generates more of these free radicals," he added. "This finding"¦ hints at a totally new mechanism of how we perceive alcohol when we drink. The conventional model basically says that alcohol affects how neurotransmitters, the molecules that communicate between neurons, do their job. But our findings suggest it is even more complex than that."

Williamson is hopeful that the results of the study, which will be published in the January 2011 issue of Alcoholism: Clinical & Experimental Research, will ultimately lead to the creation of drugs that induce CYP2E1 in order to increase a person's alcohol sensitivity prior to drinking, or help them sober up once they become inebriated.

In related news, a study conducted at the Department of Energy's (DOE) Brookhaven National Laboratory compared the effects of long-term alcohol consumption in two different types of mice--one of which lacked the brain receptor known as dopamine D2 and the other which possessed it.

According to a DOE press release, the scientists targeted the dopamine system because a deficiency in the so-called "feel good" chemical is believed to make people more vulnerable to alcoholism. Some of the mice without D2 receptors were given water, and others alcohol, and the levels of a related brain receptor--cannabinoid type 1 or CB1--were monitored. The researchers determined that under normal conditions, the absence of D2 led to increased CB1 levels, suggesting a link between the two. However, the effect was negated by chronic alcohol consumption.

"This study shows that the effects of chronic alcohol consumption on brain chemistry are critically influenced by an individual's pre-existing genetic makeup," Panayotis Thanos, a neuroscientist with the Brookhaven Lab and lead author of the study, said in a statement.

"Our findings may help explain how someone's genetic profile can interact with the environment--in this case, chronic alcohol drinking--to produce these changes only in some individuals, but not in others with a less vulnerable genetic profile," he added. "The work supports the idea that genetic screening could provide individuals with valuable information relevant to understanding risks when deciding whether or not to consume alcohol."

Like the UNC study, the DOE one is scheduled for publication in Alcoholism: Clinical & Experimental Research. Both are currently available online in the journal's Early View edition.


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