The research on genetic variation in nicotine metabolism demonstrates reproducible and clinically significant effects of nicotine metabolism rate on smoking cessation. Smokers with reduced or null activity alleles of CYP2A6 metabolize nicotine more slowly, and may experience less severe withdrawal symptoms and be more likely quit smoking (Gu et al. 2000; Kubota et al. 2006). The nicotine metabolite ratio is a reliable phenotypic measure to examine the rate of nicotine metabolism in smokers (Ray et al. 2009). Five independent studies show significant associations of this pre-treatment marker with smoking cessation and response to pharmaco-therapy (Ho et al. 2009; Lerman et al. 2010; Lerman et al. 2006; Patterson et al. 2008; Schnoll et al. 2009). There is also some support for CYP2B6 genotypes predicting smokers’ response to bupropion treatment for smoking cessation (David et al. 2007; Lee et al. 2007; Lerman et al. 2002).
