A Genetic Clue to Quitting Smoking

New genetic research helps explain why some smokers respond better to certain smoking-cessation programs than others, according to scientists at Duke University and the National Institute on Drug Abuse.

Reporting this week in the Archives of General Psychiatry, scientists describe for the first time a set of genes, about 100 in all, that seem to predict how well a smoker will respond to two different types of quitting programs — nicotine replacement or bupropion (Zyban). Nicotine-replacement methods, including the patch, pill and gum, work by weaning the smoker off nicotine gradually, usually over a period of weeks or months. Bupropion, on the other hand, is an antidepressant, which does not contain nicotine; instead, it works to curb nicotine cravings by interfering with the reward circuit in the brain, where addictions — to nicotine and other drugs, or behaviors — are reinforced. Nationally, about 70% to 80% of smokers say they want to quit, but any single attempt, regardless of the quitting method, is on average only 30% successful.

One way to boost the quitting success rate would be to match smokers with the right cessation program. A team of researchers, led by Jed Rose, director of the Duke University Center for Nicotine and Smoking Cessation Research, have begun doing just that. In their new study, the scientists screened the entire human genome and teased out a profile of genes that they think are involved in breaking nicotine addiction. Some of the genes influence basic cell communication; others code for enzymes that break down bupropion in the body. Everyone possesses all the genes in question, says Rose, but in different forms, or versions, which either amplify or dampen their effects. "We're going to see a lot more studies like this now, because the tools are there," says Dr. Normal Edelman, chief medical officer of the American Lung Association and a professor of preventive medicine at Stony Brook University. "It's a wonderful first step, because smoking cessation is a real problem — it's not easy to quit."

Rose found that people with genes that more efficiently code for bupropion breakdown respond better to the drug, while people with genetic variants that improve cell communication — also called adhesion — seem to have an easier time overall in quitting. That makes sense, since addictive behaviors such as smoking are deeply ingrained in the brain, and are strongly tied to social and environmental triggers. That network of neural connections, once cemented, is tough to break. But having certain versions of genes that facilitate neural flexibility — easing the uncoupling of certain brain connections and replacing them with new habits — could, says Rose, help people to quit smoking more quickly. "It may be that connection-forming genes are involved in the formation of addictive behaviors and in the ability to learn new behaviors that compete with and break the habit," he says. "These findings open up new, fascinating investigations into the mechanisms of addiction and how different treatments may work."

Eventually, this predictive information could come in the form of a quit-smoking "score," calculated from an individual's specific combination of different versions of the 100 or so genes that Rose's team selected. The group is also studying the genes involved in response to varenicline (Chantix), another popular smoking-cessation drug that works by blocking nicotine from binding to receptors in the brain. Even if such a test is years away, any such head start, as smokers will readily attest, would be a welcome partner in kicking the habit.