Effects of dopamine transporter and receptor polymorphisms on smoking cessation in a bupropion clinical trial.

Abstract

This study examined the role of dopaminergic genes in prospective smoking cessation and response to bupropion treatment in a placebo-controlled clinical trial. Smokers of European ancestry (N=418) provided blood samples for genetic analysis and received either bupropion or placebo (10 weeks) plus counseling. Assessments included the dopamine D2 receptor (DRD2) genotype, dopamine transporter (SLC6A3) genotype, demographic factors, and nicotine dependence. Smoking status was verified at the end of treatment (EOT) and at 6-month follow-up. The results provided evidence for a significant DRD2 * SLC6A3 interaction effect on prolonged smoking abstinence and time to relapse at EOT, independent of treatment condition. Such effects were no longer significant at 6-month follow-up, however. These results provide the first evidence from a prospective clinical trial that genes that alter dopamine function may influence smoking cessation and relapse during the treatment phase.

The functional mu opioid receptor (OPRM1) Asn40Asp variant predicts short-term response to nicotine replacement therapy in a clinical trial

“…While a few recent studies have reported evidence for the effects of inherited genetic variation on smoking cessation and response to tobacco dependence treatment, [26][27][28] the present study is the first to examine the role of the endogenous opioid system. There is a substantial body of evidence from preclinical animal and human studies implicating the endogenous opioid system, and the muopioid receptor in particular, in the reinforcing effects of nicotine administration.…”

Association of the DRD2 gene Taq1A polymorphism and smoking behavior: A meta-analysis and new data

“…A total of 28 studies published between 1994 and 2007, comprising k = 34 independent samples, were identifi ed by the search strategy, met the inclusion criteria, and contributed to the metaanalysis ( Bierut et al, 2000 ;Comings et al, 1996Comings et al, , 1997Connor et al, 2007 ;Costa-Mallen et al, 2000 ;David et al, 2007 ;Erblich, Lerman, Self, Diaz, & Bovbjerg, 2004Freire, Marques, Hutz, & Bau, 2006 ;Hamajima et al, 2002 ;Johnstone, Yudkin, Griffi ths, et al, 2004 ;Lee, 2003 ;Lerman et al, 1999Lerman et al, , 2003Morton et al, 2006 ;Noble et al, 1994 ;Preuss, Zill, Koller, Bondy, & Sokya, 2007 ;Qi, Tan, Xing, Miao, & Lin, 2002 ;Robinson et al, 2006 ;Sabol et al, 1999 ;Singleton et al, 1998 ;Spitz et al, 1998 ;Swan et al, 2005 ;Timberlake et al, 2007 ;Ton et al, 2007 ;Wu, Hudmon, Detry, Chamberlain, & Spitz, 2000 ;Yoshida et al, 2001 ). Data from the present study also were included in the meta-analysis.…”

Can the blind see? Participant guess about treatment arm assignment may influence outcome in a clinical trial of bupropion for smoking cessation

“…Participants who responded to flyers and newspaper advertisements for a free smoking cessation research program were enrolled in a double-blind pharmacogenetic bupropion smoking cessation trial approved by the Georgetown IRB between May 1999 and September 2001 Epstein et al, 2004;Lerman, Berrettini, et al, 2004;Lerman, Jepson, et al, 2006;Lerman, Roth, et al, 2002;Lerman, Shields, et al, 2002;Lerman, Shields, et al, 2003;Wileyto et al, 2004;Wileyto et al, 2005). Participants were enrolled at Georgetown University in Washington, DC, and the State University of New York at Buffalo in Buffalo, NY, and received the same treatment across the two sites.…”