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European Journal of Clinical Pharmacology

, Volume 71, Issue 9, pp 1067–1073 | Cite as

CYP2B6 rs2279343 polymorphism is associated with smoking cessation success in bupropion therapy

  • Paulo Roberto Xavier Tomaz
  • Juliana Rocha Santos
  • Jaqueline Scholz Issa
  • Tânia Ogawa Abe
  • Patrícia Viviane Gaya
  • José Eduardo Krieger
  • Alexandre Costa PereiraEmail author
  • Paulo Caleb Júnior Lima SantosEmail author
Pharmacogenetics

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.

Conclusion

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.

Keywords

Pharmacogenetics CYP2B6 gene ANKK1 gene Bupropion 

Notes

Acknowledgments

PCJL Santos is a recipient of fellowship and funding from FAPESP (Proc. 2013-09295-3 and Proc. 2013-20614-3) and from CNPq (Proc. 470410/2013-2), Brazil. PRX Tomaz is recipient of fellowship from CAPES, Brazil. JR Santos is a recipient of fellowship from CNPq, Proc. 167587/2013-7, Brazil. We also thank the patients who participated in the study. The technical assistance of the Laboratory of Genetics and Molecular Cardiology group, the FAPESP Proc. 2013/17368-0, and Sociedade Hospital Samaritano – Ministério da Saúde (PROADI-SUS; SIPAR: 25000.180.672/2011-81) are gratefully acknowledged.

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

228_2015_1896_MOESM1_ESM.docx (12 kb)
ESM 1 Linkage disequilibrium and haplotype analysis for the CYP2B6 polymorphisms in the patients submitted to treatment for smoking cessation. In a haplotype analysis, the GAC and GAT haplotypes for the CYP2B6 were associated with smoking cessation success (p values: 0.04, 0.03, respectively). (DOCX 61 kb)
228_2015_1896_MOESM2_ESM.docx (13 kb)
ESM 2 Enzymes, reagents, and fragments for the polymorphisms. (DOCX 13 kb)
228_2015_1896_MOESM3_ESM.docx (61 kb)
ESM 3 Variables of the multiple linear regression model for FTND score. (DOCX 14 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Paulo Roberto Xavier Tomaz
    • 1
  • Juliana Rocha Santos
    • 1
  • Jaqueline Scholz Issa
    • 2
  • Tânia Ogawa Abe
    • 2
  • Patrícia Viviane Gaya
    • 2
  • José Eduardo Krieger
    • 1
  • Alexandre Costa Pereira
    • 1
    • 3
    Email author
  • Paulo Caleb Júnior Lima Santos
    • 1
    • 3
    Email author
  1. 1.Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor)University of Sao Paulo Medical SchoolSao PauloBrazil
  2. 2.Smoking Cessation Program Department, Heart Institute (InCor)University of Sao Paulo Medical SchoolSao PauloBrazil
  3. 3.Laboratory of Genetics and Molecular Cardiology, Heart InstituteUniversity of Sao Paulo Medical SchoolSão PauloBrazil

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