A Gene May Discourage Drinkers from Becoming Alcoholics

Wynne Parry

Date: 19 October 2010 Time: 10:04 AM ET

Researchers have identified a gene that may protect some people from alcoholism, while making them lightweights at the bar.

It was already known that people who become inebriated easily when they begin their drinking careers are less likely to become alcoholics in the long run. Now new genetic research has zeroed in on the gene indirectly responsible for the protective effect for 10 to 20 percent of the population.

This gene, called CYP2E1, codes for an enzyme that breaks down ethanol – the intoxicating agent in alcoholic beverages – and many other toxins in the brain.

Previous work had drawn a link between this gene and the development of alcoholism, but the link was weak. It was a tough connection to make, study researcher Kirk Wilhelmsen of the University of North Carolina explained, because there are so many potential causes of alcoholism, from thrill-seeking to self-medicating for depression. This genetic study, which looked at 248 sibling pairs, found a stronger, but less direct connection.

CYP2E1 has a "big effect on how the brain perceives alcohol, and we know that's a reason people can become alcoholics," Wilhelmsen told LiveScience.

It turns out that for people who are sensitive to alcohol, changes in the gene prompt their bodies to churn out more of the enzyme that breaks down alcohol, producing free radicals, which are highly reactive atoms. (Most alcohol is metabolized in the liver, where it is treated like sugar and broken down to produce energy.)

It's not known why high sensitivity to alcohol indicates a reduced risk of alcoholism later on, but Wilhelmson said it may be analogous to the flush some people, particularly Asians, experience after drinking. Just as the unpleasant flush may discourage chronic drinking, those who are highly sensitive may learn moderation, he said.

The study enrolled undergraduate students, most of whom had at least one alcoholic parent. These participants – relatively inexperienced drinkers – were given the equivalent of about three drinks and asked to assess how the alcohol made them feel. The sway in their posture and the alcohol on their breath were also measured.

The researchers also determined the genetic sequence of specific spots in the participants' DNA where individual variations are common, and used this information to make genetic comparisons between the siblings and among the subjects as a whole.

They were able to associate the presence of at least one copy of a relatively rare version of the CYP2E1 gene with the more intense responses to alcohol – those students who reported feeling more drunk than others.

The gene is also connected to nicotine metabolism, as well as higher incidences of cancer, which may be explained by the free radicals the enzyme produces when it breaks alcohol down, since these can damage DNA, according to Wilhelmsen.

The study appears in today's online edition (Oct. 19) of the journal Alcoholism: Clinical and Experimental Research.