Paulo Roberto Xavier Tomaz1, Mariana Soares Kajita2, Juliana Rocha Santos1, Jaqueline Scholz3, Tânia Ogawa Abe3, Patrícia Viviane Gaya3, José Eduardo Krieger1, Alexandre Costa Pereira1, Paulo Caleb Júnior Lima Santos4. 1. Laboratory of Genetics and Molecular Cardiology, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil. 2. Department of Pharmacology-Escola Paulista de Medicina, Universidade Federal de Sao Paulo EPM-Unifesp, São Paulo, Brazil. 3. Smoking Cessation Program Department, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil. 4. Department of Pharmacology-Escola Paulista de Medicina, Universidade Federal de Sao Paulo EPM-Unifesp, São Paulo, Brazil. paulo.caleb@unifesp.b.
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.
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 CYP2A6rs1801272 and rs28399433 and CYP2B6rs8109525 polymorphisms were genotyped by real-time PCR using the TaqMan® platform. RESULTS:Patients with AG or GG genotypes for CYP2B6rs8109525 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:CYP2B6rs8109525 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.
Authors: S A Ribeiro; J R Jardim; R R Laranjeira; A K Alves; F Kesselring; L Fleissig; M Z Almeida; M Matsuda; R S Hamamoto Journal: Rev Assoc Med Bras (1992) Date: 1999 Jan-Mar Impact factor: 1.209
Authors: Jane E Sarginson; Joel D Killen; Laura C Lazzeroni; Stephen P Fortmann; Heather S Ryan; Alan F Schatzberg; Greer M Murphy Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2011-01-25 Impact factor: 3.568
Authors: Caryn Lerman; Robert A Schnoll; Larry W Hawk; Paul Cinciripini; Tony P George; E Paul Wileyto; Gary E Swan; Neal L Benowitz; Daniel F Heitjan; Rachel F Tyndale Journal: Lancet Respir Med Date: 2015-01-12 Impact factor: 30.700
Authors: David P King; Sara Paciga; Eve Pickering; Neal L Benowitz; Laura J Bierut; David V Conti; Jaakko Kaprio; Caryn Lerman; Peter W Park Journal: Neuropsychopharmacology Date: 2011-11-02 Impact factor: 7.853
Authors: A Joseph Bloom; Maribel Martinez; Li-Shiun Chen; Laura J Bierut; Sharon E Murphy; Alison Goate Journal: PLoS One Date: 2013-11-15 Impact factor: 3.240