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Bum Enzymes Cut Cigarette Cravings

Some people who try smoking cigarettes never become addicted. Now scientists have found that these people are less susceptible to tobacco addiction because their bodies break down less of its addictive component, nicotine. The findings, reported in tomorrow's issue of Nature, may lead to drugs that block nicotine metabolism and help addicted smokers quit.

In past studies targeting the molecular roots of nicotine addiction, pharmacologist Rachel Tyndale of the University of Toronto and her colleagues identified an enzyme, called CYP2A6, that breaks down more than 48% of the nicotine from smoking. Because an estimated 18.5% of the population carries one or two defective copies of the CYP2A6 gene and can't metabolize nicotine well, the team wondered if these people were protected from nicotine addiction. That's because addicts crave nicotine because their bodies are so efficient at breaking down the chemical.

To see which versions of the CYP2A6 enzyme smokers carry, the researchers extracted CYP2A6 genes from the white blood cells of 244 smokers and from 184 people who had tried cigarettes but who, not having developed a habit, became nonsmokers. After making millions of copies of the genes, they sorted them with enzymes that cut the variants into different sizes. The researchers found that nonsmokers who had not become addicted were 51% more likely to have defective CYP2A6 variants than smokers. Smokers with defective CYP2A6 enzymes smoked 23% fewer cigarettes each week, suggesting that inhibitors of these enzymes may one day help smokers cut down on the number of cigarettes they smoke.

"This is the first study that demonstrates a genetic mechanism that could render you more vulnerable to nicotine addiction," says Alan Leshner, director of the National Institute on Drug Abuse. The enzymes may also help explain why some smokers just can't quit cold turkey, says oral pathologist Brad Rodu of the University of Alabama, Birmingham. The fact that drugs that block CYP2A6 may help these "inveterate smokers" cut down and quit, Rodu adds, "is very exciting and very interesting."