Dopamine receptor DRD2 genotype and smoking cessation outcome following treatment with bupropion SR

Abstract

The A1 allele of the dopamine D2 receptor gene (DRD2) is associated with a reduced number of dopamine binding sites in the brain and with the increased likelihood of substance abuse and addictive behavior. In a study of smokers enrolled in an open-label, randomized effectiveness trial, we investigated whether variants in the DRD2 receptor gene are associated with smoking cessation outcomes following treatment with a combination of bupropion SR and behavioral counseling. Adherence to treatment and pointprevalent smoking status were assessed at 3 and 12 months, respectively, following a target quit date. Compared to women who carry both A2 alleles, women with at least one A1 allele were more likely to report having stopped taking bupropion due to medication side effects (odds ratio (OR) ¼ 1.91, 95% confidence interval (CI) ¼ 1.01-3.60; Po0.04) and at 12 months were somewhat more likely to report smoking (OR ¼ 0.76, 95% CI ¼ 0.56-1.03; Po0.076). Significant associations or trends were not observed in men. In women, individual variability in responsiveness to bupropion-based treatment may be partially due to differences in genetic variants influencing dopamine receptor function. INTRODUCTIONTobacco use remains the major preventable cause of premature disability and death in developed countries. Despite best efforts to date, 46 million people still smoke in the United States, and over 440 000 people die each year from tobaccorelated illness; the estimated smoking-related cost to the economy is $157 billion annually.1 Effective pharmacologic interventions for smoking cessation include several forms of nicotine replacement and the use of the antidepressant medication, bupropion.2 Despite treatment advances, smoking relapse after successful intervention for smoking cessation occurs in 70 to 80% of patients within 12 months. [3][4][5] Still to be determined is why some people remain nonsmokers after pharmacologic intervention and others do not.The dopaminergic mesocorticolimbic pathway in the brain is thought to play an important role in tobacco and nicotine addiction. [6][7][8] The TaqIA polymorphism of the dopamine D2 receptor gene (DRD2) results from a C/T

Interaction between variation in the D2 dopamine receptor (DRD2) and the neuronal calcium sensor-1 (FREQ) genes in predicting response to nicotine replacement therapy for tobacco dependence

“…5 Our findings indicate that smokers homozygous for the DRD2 À141 Ins benefit more from bupropion treatment and persons with Ins/Del or Del/ Del genotypes at the DRD2À141 locus respond better to behavioral counseling or NRT. 5 Results from this study and others [6][7][8] may, in the future, help practitioners maximize the therapeutic benefit of pharmacological treatments for nicotine dependence.…”

Overview of the pharmacogenomics of cigarette smoking

“…212 Conversely, women with the TaqI A1 genotypes appear to do worse on bupropion, reporting more side effects and relapse at 12 months follow-up. 213,214 There is evidence the À141C Ins/Del variant in DRD2, which has been associated with increased transcriptional activity in vitro, 215 is predictive of outcomes to NRT or bupropion. Subjects homozygous for the À141C Ins allele…”

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

“…therapy (NRT) Lerman et al, 2006 ;Yudkin et al, 2004 ), whereas increased-function alleles (e.g., Taq1A2) have been reported to predict better response to bupropion ( David et al, 2007 ;Lerman et al, 2006 ;Swan et al, 2005 ). Nevertheless, some studies have failed to demonstrate an effect of DRD2 genotype on smoking cessation ( Berlin, Covey, Jiang, & Hamer, 2005 ).…”

“…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.…”