Effect of genetic polymorphisms on smoking cessation: a trial of bupropion in Korean male smokers

Abstract

Background Even though bupropion is first-line pharmacological agent for smoking cessation, not all the smokers successfully quit smoking by bupropion. It means other factors like genetic predisposition could contribute to the therapeutic outcome. Objectives The aim of this study is to elucidate the question of whether the abstinence rates by bupropion trial would be different depending on the genotypes. Methods Six candidate genes, thought to be involved in the interaction of nicotine and bupropion (for example, the dopamine receptor type 2, dopamine transporter, norepinephrine transporter, serotonin transporter, catecholamine-O-methyltransferase), and the clinical outcomes of smoking behavior were investigated. The participants were 225 male smokers to whom 150 mg of bupropion SIR was administered for 4 weeks. The abstinence rates of specific genotypes were also compared. were higher in the abstinence group than in the nonabstinence group (chi(2) =8.12,P=0.02 for COMTH/ COMTH, chi(2) = 3.04, P < 0.01 for A/G). (b) Participants having specific genotypes such as homozygotes; (A1/A1 or A2/ A2) of DRD2 Taql A, COMTH/COMTH, AG of NET-8, and LL of 5-HTTLPR showed a higher abstinence rate than the other participants. Conclusions It can be concluded that genetic diversity might determine the effects of bupropion on smoking cessation. Main results The results are as follows: (a) the frequencies of the A1/A2 genotype of the dopamine receptor type 2 Taql A gene and SLC6A3-9 genotype of the dopamine transporter 1 gene were higher in the nonabstinence group than in the abstinence group (chi(2) = 20.40, P < 0.01 for A1/A2, chi(2) =7.76, P=0.01 for SLC6A3-9). The frequencies of the COMTH/COMTH and A/G genotypes of the norepinephrine transporter gene were higher in the abstinence group than in the nonabstinence group (chi(2) =8.12,P=0.02 for COMTH/ COMTH, chi(2) = 3.04, P < 0.01 for A/G). (b) Participants having specific genotypes such as homozygotes; (A1/A1 or A2/ A2) of DRD2 Taql A, COMTH/COMTH, AG of NET-8, and LL of 5-HTTLPR showed a higher abstinence rate than the other participants. Conclusions It can be concluded that genetic diversity might determine the effects of bupropion on smoking cessation.