Gene Variants Impact Smokers' Response to Cessation Therapy

High-risk haplotypes predict later age of smoking cessation; interact with treatment to affect success

FRIDAY, June 1 (HealthDay News) -- Smokers with certain high-risk genetic variants find it more difficult to quit smoking but are more likely to respond to cessation pharmacotherapy, according to a study published online May 30 in the American Journal of Psychiatry.

Li-Shiun Chen, M.D., M.P.H., Sc.D., from the Washington University School of Medicine in St. Louis, and colleagues analyzed three common haplotypes in the CHRNA5-CHRNA3-CHRNB4 region associated with nicotine dependence in 5,216 smokers in the community and 1,073 smokers in a smoking cessation clinical trial.

The researchers found that, in the community-based sample, haplotypes that predicted nicotine dependence were associated with smoking cessation at a later age. For individuals receiving placebo, but not active medication, these variants predicted abstinence at the end of treatment. The success of cessation was affected by the interaction of genetic variants with treatment.

"Smokers with the high-risk haplotype were three times as likely to respond to pharmacologic cessation treatments as were smokers with the low-risk haplotype," Chen and colleagues conclude. "The high-risk variants increase the risk of cessation failure, and this increased risk can be ameliorated by cessation pharmacotherapy. By identifying a high-risk genetic group with heightened response to smoking cessation pharmacotherapy, this work may support the development of personalized cessation treatments."

Glaxo Wellcome provided the study drug at no cost. Several authors are listed as inventors on a patent covering the use of certain small nucleotide polymorphisms in determining the diagnosis, prognosis, and treatment of addiction.

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