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


OBJECTIVE
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 SR was administered for 4 weeks. The abstinence rates of specific genotypes were also compared.


RESULTS
The results are as follows: (a) the frequencies of the A1/A2 genotype of the dopamine receptor type 2 TaqI A gene and SLC6A3-9 genotype of the dopamine transporter 1 gene were higher in the nonabstinence group than in the abstinence group (chi2=20.40, P<0.01 for A1/A2, chi2=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 (chi2=8.12,P=0.02 for COMTH/COMTH, chi2=3.04, P<0.01 for A/G). (b) Participants having specific genotypes such as homozygotes (A1/A1 or A2/A2) of DRD2 TaqI 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.
Han
Doug-Hyun
DH
Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Joe
Keun-Ho
KH
Na
Chul
C
Lee
Young-Sik
YS
D000328:Adult; D044466:Asian People / Q000235:genetics*; D016642:Bupropion / Q000494:pharmacology*; D003710:Demography; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007723:Korea; D008297:Male; D011110:Polymorphism, Genetic; D016540:Smoking Cessation; D017211:Treatment Failure
D016642:Bupropion