Profile of the Nicotinic Cholinergic Receptor Alpha 7 Subunit Gene Expression is Associated with Response to Varenicline Treatment

Author(s)

Santos, Juliana Rocha ^[1] ; Xavier Tomaz, Paulo Roberto ^[1] ; Scholz, Jaqueline Ribeiro ^[2] ; Gaya, Patricia Viviane ^[2] ; Abe, Tania Ogawa ^[2] ; Krieger, Jose Eduardo ^[1] ; Pereira, Alexandre Costa ^[1] ; de Lima Santos, Paulo Caleb Junior ^[3]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Genet & Mol Cardiol, Inst Coracao InCor, BR-05403904 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Smoking Cessat Program Dept, Inst Coracao InCor, BR-05403904 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Pharmacol, Escola Paulista Med, EPM Unifesp, BR-04044020 Sao Paulo - Brazil

• Document type: Journal article
• Source: GENES; v. 11, n. 7 JUL 2020.
• Web of Science Citations: 1

Abstract

Introduction: Smoking is considered the leading cause of preventable morbidity and mortality worldwide. Studies have sought to identify predictors of response to smoking cessation treatments. The aim of this study was to analyze a possible association of target gene expression for smoking cessation with varenicline. Methods: We included 74 smokers starting treatment with varenicline. Gene expression analysis was performed through the custom RT2 Profiler qPCR array assay, including 17 genes. Times for sample collection were before the start of therapy (T0) and two weeks (T2) and four weeks (T4) after the start of treatment. Results: For gene expression analysis, we selected 14 patients who had success and 13 patients resistant to varenicline treatment. Success was considered to be when a patient achieved tobacco abstinence until the fourth week of treatment and resistant was when a patient had not stopped smoking as of the fourth week of treatment. We observed a significant difference forCHRNA7gene expression: in the resistant group, samples from T2 and T4 had lower expression compared with T0 (fold change: 0.38,P= 0.007; fold change: 0.67,P= 0.004; respectively). Conclusion: This exploratory clinical study, searching for a possible predictor of effectiveness for varenicline, reaffirmed the association of the alpha 7 nAChR subunit for nicotine dependence and smoking therapy effectiveness with varenicline. (AU)

• FAPESP's process: 13/09295-3 - Pharmacogenetic of cardiovascular system drugs focusing on implementation
• Grantee: Paulo Caleb Júnior de Lima Santos
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/08338-7 - Pharmacogenomics: implementation and cost-effectiveness evaluation
• Grantee: Paulo Caleb Júnior de Lima Santos
• Support Opportunities: Regular Research Grants