Gene Variant Found That Can Help Protect Against Nicotine Addiction

June 24, 1998

Some individuals carry a gene variant that may help protect them from becoming addicted to nicotine, according to a new study funded in part by the National Institute on Drug Abuse, National Institutes of Health, and published in the June 25 issue of Nature. The study found that individuals with a genetic variant in a particular enzyme break nicotine more slowly than those who do not. They have greater resistance to nicotine addiction and, if they do smoke, they smoke fewer cigarettes than individuals without the impairment.

Nicotine, the addictive component in tobacco products, is metabolized or broken down primarily by an enzyme in the liver known as CYP2A6. In this study, University of Toronto researchers, led by Dr. Rachel F. Tyndale, observed that variations in the gene for CYP2A6 affect how individuals metabolize nicotine. People with decreased functional CYP2A6 are less likely to become addicted to it.

Dr. Alan I. Leshner, Director of NIDA, said, "We are very excited about the findings from this study and its implications for understanding and treating nicotine addiction. We have long known that individuals vary in their vulnerability to becoming addicted, and this study identifies one gene involved in those individual differences. In addition, understanding the critical role this enzyme plays in nicotine addiction gives a new target for developing more effective medications to help people stop smoking."

Researchers found three different gene types (alleles) for the enzyme CYP2A6, including a normal, or wild-type allele that is fully functional, and two null or inactive alleles. People with the null alleles functionally lack the enzyme and are unable to break down nicotine to cotinine. When comparing a group of smokers to a group that had tried tobacco but had never become addicted to it, they found individuals in the non-addicted group were much more likely to have impaired nicotine metabolism (and to have one null allele for CYP2A6). Thus, those with a null allele had been "protected" against nicotine addiction compared with individuals with the normal or wild type alleles. In addition, among a group of people who do smoke regularly, those with null CYP2A6 alleles smoked fewer cigarettes over the course of a week than those with normal CYP2A6 alleles.

Dr. Tyndale said, "These two factors, a reduced propensity to smoke and the need to smoke less, would likely decrease the risk of developing tobacco-related illnesses, such as cancer, among those with CYP2A6-null alleles."

The University of Toronto team notes that nicotine from sources other than cigarettes would also be affected by the impaired enzyme, which might allow most over-the-counter nicotine replacement therapies (patch, gum, spray) to be better utilized. The team concludes that the protective effect of CYP2A6-null alleles suggests that medications might be developed that can inhibit the enzyme, thus providing innovative approaches to preventing and treating nicotine addiction.

The use of nicotine products is a major preventable cause of death in the United States. About 62 million Americans age 12 and over are current cigarette smokers, making nicotine one of the most heavily used addictive drugs. The scientific facts about nicotine addiction, based on the latest research, will be the focus of Addicted to Nicotine: A National Research Forum, to be held July 27-28, 1998. The conference, sponsored by NIDA and the Robert Wood Johnson Foundation and cosponsored by the National Cancer Institute and the Centers for Disease Control and Prevention's Office on Smoking and Health, will highlight the sources of nicotine addiction, prevention of tobacco product use, and state-of-the-art treatment strategies. The conference will be held at the Natcher Auditorium on the NIH Campus in Bethesda, MD. For more information, contact the NIDA Press Office.

NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute also carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on health effects of drugs of abuse and other topics can be ordered free of charge in English and Spanish, by calling NIDA Infofax at 1-888-NIH-NIDA (-644-6432) or 1-888-TTY-NIDA (-889-6432) for the deaf. These fact sheets and further information on NIDA research and other activities can be found on the NIDA home page at


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