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Quitting may be tougher for smokers with “craving” gene
  
By
Edward R. Winstead


Smokers who possess a particular variant of a gene that seems to be associated with a craving for tobacco may be more likely to relapse after a treatment program than smokers without the variant, a new study has found.


The study also found that smokers with the gene variant may benefit from taking the drug bupropion, which is used to treat depression as well as to help smokers quit.

Bupropion is sold as Wellbutrin to treat depression; Zyban is a sustained release form of Wellbutrin that was approved specifically for smoking cessation.

Overall, women in the study responded well to bupropion treatment, which is noteworthy because most anti-smoking treatments, such as nicotine replacement therapy, tend to benefit males more than females.

"There is a vast literature on gender differences in smoking cessation," says Caryn Lerman of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia, who led the research. "This study suggests that bupropion may be particularly effective for women trying to quit smoking who have the genetic predisposition."

The genetic predisposition comes from having a version of the CYP2B6 gene, which is involved in metabolizing both nicotine and bupropion. The gene variant is less active than other forms of the gene, which may in turn affect how nicotine is metabolized in the brain.

"Smokers who had the genetic variant had a greater increase in cravings after they quit," says Lerman. "And they were more likely to relapse than smokers without the variant."

The study's 426 smokers—both men and women—received bupropion or a placebo, plus seven group counseling sessions. Researchers monitored on a weekly basis whether the subjects were smoking and experiencing symptoms or side effects from the treatment. They were evaluated at the end of the treatment program and again six months later.

Among women with the genetic variant, 54 percent of those treated with bupropion were abstinent at the end of the study, compared to 19 percent of those who received a placebo.

The findings will need to be replicated in larger populations before they can be used to inform decisions about treatment. But the study points to new avenues of research, such as the effectiveness of bupropion in helping female smokers with the variant quit.

The genetic basis of smoking is a hot topic among researchers, says Lerman, adding that the field has yet to produce conclusive findings. The new study appears in Pharmacogenetics.

"Smoking is a complex behavior that probably involves dozens of genes," she says. "We need larger studies to examine the interactions between numerous genes and the social, psychological and environmental factors that influence smoking."

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Lerman, C. et al. Pharmacogenetic investigation of smoking cessation treatment. Pharmacogenetics 12, 627-634 (November 2002).
 

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