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| |  Gene Polymorphism May Affect Efficacy of Bupropion for Smoking Cessation: Presented at SRNT By Liz Meszaros BALTIMORE, Md -- February 26, 2010 -- Bupropion treatment for smoking cessation may be more effective in smokers who have a risk-related variant -- the long variable number of tandem repeats (VNTR) allele in exon-3 of the dopamine D4 receptor gene (DRD4) -- than those who do not, according to a study presented here on February 25 at the 2010 Society for Research on Nicotine and Tobacco (SRNT) Annual Meeting. “Dopamine is a neurotransmitter that is involved in addiction and is affected by bupropion,” said Adam Leventhal, PhD, Division of Health Behavior Research, University of Southern California Keck School of Medicine, Los Angeles, California. “Thus, genes in the dopamine system, such as the DRD4 gene, are logical candidates for identifying predictors of bupropion’s effectiveness.” To explore this possibility, Dr. Leventhal and colleagues studied 334 smokers (>10 cigarettes/day). Patients were randomised in a double-blinded design to receive bupropion sustained-release (SR) tablets or placebo plus counselling for smoking cessation for 12 weeks. Alleles were classified as long (L) if they consisted of 7 or more repeats, or short (S) for 6 or fewer repeats. Patients were grouped into those with at least 1 copy of the L allele (SL+LL) versus those with no copies (SS). Bupropion was associated with an increased odds of abstinence compared with placebo (P = .13). In addition, a significant interaction between DRD4 and bupropion was found (P = .006). Bupropion had significant effects on smoking cessation in SL+LL smokers (P < .0001). However, it did not have a significant effect on smoking cessation among SS smokers (P = .28). Abstinence rates in the SL+LL group at end of treatment were 60% in the bupropion group versus 21% in the placebo group (P < .0001). These rates in the SS group at end of treatment were 55% versus 42%, respectively (P = .04). When gender and depression severity were controlled for, the DRD4 bupropion interaction remained significant (P = .005). “Although bupropion is a front-line treatment for smoking cessation, evidence suggests that it is only effective for a proportion of smokers,” said Dr. Leventhal. “Identifying genes that predict who will respond best to bupropion could provide insights about etiology of tobacco addiction; and potentially guide the development of personalised medicine approaches in which specific treatments are tailored to an individual’s genetic makeup.” “If these findings are replicated and extended, they could eventually be used to develop pharmacogenomic treatment approaches in which clinicians can select bupropion versus other treatments for smokers based on their genotype for the DRD4 gene and other genetic variants known to predict medication response,” he concluded. Funding for this study was provided by the National Institutes of Health. [Presentation title: Dopamine D4 Receptor Gene Exon-III VNTR Polymorphism Moderates the Efficacy of Bupropion for Smoking Cessation. Abstract POS2-16]
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