Nicotine addiction may be in the genes

Copyright 1998 Associated Press
June 24, 1998


NEW YORK - Scientists say they have identified a gene that helps protect some people from getting hooked on cigarettes. If confirmed, the finding might lead to medications that help smokers cut back or quit.

About one-fifth of the nonsmoking population carries a protective version of the gene, said Rachel Tyndale, one of the study's authors. The gene's influence might have saved some 7 million current residents of North America from nicotine addiction, she said.

It is at least the second gene thought to play a role in vulnerability to nicotine addiction. But genetics experts warned that the case for the new gene is far from proven.

Tyndale and colleagues at the University of Toronto in Ontario, Canada, report their findings in Thursday's issue of the journal Nature.

Dr. Neal Benowitz, a nicotine researcher at the University of California at San Francisco, said the result makes sense biologically. But he cautioned that in the past, similar initial findings of addiction genes have not been confirmed by further research.

Nonetheless, he called the finding an important early step in finding out why some people are more vulnerable to nicotine addiction than others. Only about a third of young people who experiment with cigarettes get hooked, and ''we don't know why,'' Benowitz said.

He and others said the answer will be much more complex than one or two genes.

Prior research has implicated a gene involved in the brain's dopamine communication system. People with a certain variant of the gene start smoking at a younger age, get hooked earlier and find it harder to quit.

The gene in the new study tells the body how to make an enzyme called CYP2A6 that breaks down nicotine. Defective forms of this gene lead to a defective version of the enzyme, impairing the body's ability to process nicotine.

Everybody inherits two copies of the gene, and the study suggests that getting even one bad copy offers some protection against getting hooked.

Researchers studied 244 nicotine-dependent smokers and 184 people who had tried smoking but never got hooked.

The researchers found at least one bad copy of the gene in 12% of dependent smokers vs. 19% of the others. The difference suggests that bad copies discourage people from getting hooked.

The study also found that among the 164 smokers who were hooked on tobacco but not alcohol, those with even one bad copy of the gene smoked fewer cigarettes, an average of 129 a week vs. 159.

This suggests that if scientists can come up with pills that block the action of the CYP2A6 enzyme, the medications could help smokers cut back, Tyndale said. Such pills might also help smokers avoid relapse if they've quit already, she said.

Tyndale said defective copies of the gene could reduce cigarette consumption by making smokers break down nicotine more slowly. Since the nicotine sticks around longer, smokers need fewer cigarettes to maintain a satisfying nicotine level, she said.

As for why the genetic defect would make a person less likely to get hooked, Tyndale noted that nicotine initially makes a neophyte smoker dizzy and nauseous. People get hooked only if they persist in smoking despite the discomfort, she said. If a person breaks nicotine down unusually slowly, it will stick around and make those initial experiences more uncomfortable, making it more likely the person will give up, she theorized.

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