Pharmacogenetics of smoking cessation therapy

Abstract

Nicotine dependence is a major health problem, with a large amount of smoking-related premature deaths and disabilities. The dependence mechanism of nicotine is especially complex and is under strong genetic influence. Smoking cessation is associated with substantial health benefits. Evidence from animal and human studies suggests that genetic polymorphisms influencing pharmacokinetics and pharmacodynamics of nicotine may have great potential for aiding smoking treatment. There are more than 30 association studies and one genome-wide association study (GWAS) between genetic polymorphisms and smoking cessation following nicotine replacement therapy (NRT) and/or bupropion therapy. However, only a few candidate genes or regions were analyzed more than twice and even these genes require additional investigations in different therapeutic schemes. There are a growing number of new pharmacologic options that have not been pharmacogenetically assessed according to published literature. In addition, molecular genetics studies are needed to assess the functional mechanisms of some putative association results. Taken together, the preliminary findings are promising but raise the need for new studies with adequate sample sizes and adjustment for several potential confounding factors frequently neglected, such as comorbidity and sociodemographic factors. The current state of the art in the field encourages an optimist view that personalized treatment approaches may become possible. However, the current scientific evidence still does not support the use of pharmacogenetic tests in routine smoking cessation therapy.