title: CYP2B6 rs2279343 polymorphism is associated with smoking cessation success in bupropion therapy.
abstract: BACKGROUND
  Previous studies suggested that polymorphisms in the CYP2B6 gene (which encodes an isoenzyme that metabolizes bupropion) and in the ANKK1 gene (which is located in the ANKK1/DRD2 gene cluster) might influence response to therapy. Thus, the aim of the present study was to evaluate whether the CYP2B6 and ANKK1 polymorphisms are associated with the response to smoking cessation therapies in patients from a smoking cessation assistance program.
  
  
  METHODS
  The cohort study enrolled 478 smokers who received behavioral counseling and drug therapy (bupropion, nicotine replacement therapy, and/or varenicline). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. Fagerström test for nicotine dependence (FTND) and Issa situational smoking scores were analyzed for nicotine dependence (ND). The ANKK1 rs1800497, CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371), and CYP2B6*9 (rs3745274) polymorphisms were genotyped by high resolution melting analysis or by restriction fragment length polymorphism.
  
  
  RESULTS
  Patients with CYP2B6 rs2279343 wild-type AA genotype had higher success rate (48.0 %) compared with patients carrying AG or GG genotypes (CYP2B6*4 variant) (35.5 %) on bupropion therapy. The AA genotype was associated with higher OR for success during bupropion therapy (OR = 1.92, 95 % CI = 1.08-3.42, p = 0.03) in a multivariate model. We did not observe significant differences in the FTND and Issa scores according to the studied polymorphisms.
  
  
  CONCLUSIONS
  We showed that patients with CYP2B6*4 (rs2279343) variant had lower success rate with bupropion. Likely, the CYP2B6*4 variant, which leads to a rapid predicted metabolic phenotype for the isoenzyme, influences the pharmacological activity of bupropion. Our finding suggests that CYP2B6*4 may be an important genetic marker for individualized bupropion pharmacotherapy.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Paulo Roberto Xavier
authors.initials: PR
authors.lastname: Tomaz
authors.forename: Juliana Rocha
authors.initials: JR
authors.lastname: Santos
authors.forename: Jaqueline Scholz
authors.initials: JS
authors.lastname: Issa
authors.forename: Tânia Ogawa
authors.initials: TO
authors.lastname: Abe
authors.forename: Patrícia Viviane
authors.initials: PV
authors.lastname: Gaya
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
authors.forename: Paulo Caleb Júnior Lima
authors.initials: PC
authors.lastname: Santos
mesh_terms: D016642:Bupropion / Q000494:pharmacology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003376:Counseling; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016540:Smoking Cessation / Q000379:methods* / Q000523:psychology; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D016896:Treatment Outcome; D000068580:Varenicline / Q000627:therapeutic use
chemical_list: D016642:Bupropion; D065702:Cytochrome P-450 CYP2B6; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases; D000068580:Varenicline