Cytochrome P450 2A6 and 2B6 polymorphisms and smoking cessation success in patients treated with varenicline
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.
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.
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).
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.
KeywordsCYP2A6 CYP2B6 Nicotine metabolism Smoking cessation Polymorphism rs8109525
We thank the patients who participated in the study and the technical assistance of the Laboratory of Genetics and Molecular Cardiology group.
Authorship and author responsibilities
PRXT, MK, JRS, and PCJLS carried out the molecular genetic and statistical analysis and drafted the manuscript. PCJLS, JS, TOA, PVG, JEK, and ACP participated in the design of the study and ceded the facilities. JS, TOA, and PVG selected the patients. All authors contributed critically to the manuscript, whose present version was read and approved by all.
We thank the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo, Brazil)—Proc. 2013/09295-3 and CNPq (Proc. 470410/2013-2), Brazil. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 (PRX Tomaz and JR Santos are recipients of fellowships from CAPES, Brazil). Sociedade Hospital Samaritano—Ministério da Saúde (PROADI-SUS; SIPAR: 25000.180.672/2011-81).
Compliance with ethical standards
Written informed consent was obtained from all participants prior to entering the study (CAPPESQ no. 0022/11—SDC: 3579/10/168).
Conflict of interest
The authors declare that they have no conflict of interest.
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