Cytochrome P450 2A6 and 2B6 polymorphisms and smoking cessation success in patients treated with varenicline

Eur J Clin Pharmacol. 2019 Nov;75(11):1541-1545. doi: 10.1007/s00228-019-02731-z. Epub 2019 Aug 11.

Abstract

Background: The identification of variants in genes involved in nicotine metabolism may have implications for the pharmacological therapy of smoking. In the scenario of precision medicine, the aim of this study was to evaluate a possible association of cytochrome P450 2A6 and 2B6 polymorphisms with varenicline pharmacotherapy.

Methods: The present study included 167 patients treated with varenicline in monotherapy who were from a cohort study of 1049 patients (treated with smoking cessation drugs: nicotine replacement therapy, bupropion, varenicline, or combinations of same). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. The CYP2A6 rs1801272 and rs28399433 and CYP2B6 rs8109525 polymorphisms were genotyped by real-time PCR using the TaqMan® platform.

Results: Patients with AG or GG genotypes for CYP2B6 rs8109525 had a higher success rate of smoking cessation with varenicline (51.2%) compared with carriers of the AA genotypes (33.3%, P = 0.03, n = 167). The AG or GG genotypes were also associated with a higher odds ratio of success, even in a multivariate analysis adjusting for potential confounders (OR = 2.01; 95%CI = 1.01 to 4.00; P = 0.047).

Conclusion: CYP2B6 rs8109525 was associated with a higher success rate of smoking cessation with varenicline treatment. This finding may be useful in pharmacogenomic strategies for smoking cessation therapy.

Keywords: CYP2A6; CYP2B6; Nicotine metabolism; Polymorphism; Smoking cessation; rs8109525.

MeSH terms

  • Adult
  • Cytochrome P-450 CYP2A6 / genetics
  • Cytochrome P-450 CYP2B6 / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Smoking / drug therapy*
  • Smoking / genetics
  • Smoking Cessation / statistics & numerical data*
  • Smoking Cessation Agents / therapeutic use*
  • Treatment Outcome
  • Varenicline / therapeutic use*

Substances

  • Smoking Cessation Agents
  • CYP2A6 protein, human
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 CYP2B6
  • Varenicline