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

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 for CHRNA7 gene 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 α7 nAChR subunit for nicotine dependence and smoking therapy effectiveness with varenicline.