Effects of dopamine transporter and receptor polymorphisms on smoking cessation in a bupropion clinical trial.
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.
University of Pennsylvania, Dept of Psychiatry, Abramson Cancer Ctr, Philadelphia, PA 19104, USA. clerman@mail.med.upenn.edu
Caryn
C
Lerman
Peter G
PG
Shields
E Paul
EP
Wileyto
Janet
J
Audrain
Larry H
LH
Hawk
Angela
A
Pinto
Susan
S
Kucharski
Shiva
S
Krishnan
Ray
R
Niaura
Leonard H
LH
Epstein
D016642:Bupropion / Q000627:therapeutic use*; D004219:District of Columbia; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins; D009518:New York; D010919:Placebos; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics; D016540:Smoking Cessation / Q000208:ethnology / Q000379:methods*; D044465:White People / Q000235:genetics*
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010919:Placebos; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D016642:Bupropion