Genetic makeup may detemine likely success of quit smoking therapies

Aug 30 2005

A study by researchers at the Transdisciplinary Tobacco Use Research Center (TTURC) of the University of Pennsylvania School of Medicine indicates that a smoker's genetic make-up may affect whether they quit or not while using either bupropion (Zyban) or nicotine replacement therapies (NRTs) such as the nicotine patch or nasal spray.

The results appear in the August issue of Neuropsychopharmacology.

"This study provides new evidence that genetic differences in the brain-reward pathways of smokers may reveal whether they would benefit more from Zyban or nicotine replacement therapy as an aid to quitting smoking," said lead author Professor Caryn Lerman, PhD, Director of the TTURC and Associate Director for Cancer Control Population Sciences at Penn's Abramson Cancer Center.

Lerman led a research team that completed two randomized clinical trials each with a six-month follow-up period: a double blind placebo-controlled trial of bupropion and an open-label trial of transdermal nicotine patch versus nicotine nasal spray. Both trials examined the roles of functional genetic variation in the dopamine D2 Receptor (DRD2) gene called DRD2 –141C. At this location in the DRD2 gene, people carry one of two different variants, a Del C variant or an Ins C variant (Del is for deletion and Ins is for Insertion). The research team found that smokers with two copies of the DRD2 -141 Ins C variant were significantly more likely to be abstinent at the six-month follow-up if they used

Zyban, as compared to smokers carrying the Del C variant. By contrast, smokers carrying the Del C variant had significantly higher quit rates if they used NRTs as compared to those with the Ins C variant. This research may have important implications for the delivery of quit-smoking medications that are targeted to individual smokers' needs. "Although these results require confirmation in a larger study prior to translation to practice," said Lerman, "they do suggest that genetic information may be useful in selecting the type of nicotine dependence treatment that will be most beneficial for a particular smoker."