Variation in nicotine metabolism rate can also be determined by the ratio of the nicotine metabolites (3-HC/cotinine) that is derived from cigarette smoking (Benowitz et al. 2003). The ratio of 3-HC/cotinine is generally referred to as the nicotine metabolite ratio and can be measured reliably in saliva or plasma (Dempsey et al. 2004) and is independent of smoking patterns or time since last cigarette, among regular smokers (Levi et al. 2007). Null or reduced activity CYP2A6 alleles (CYP2A6*2, *4, *9, and *12) are associated with lower nicotine metabolite ratios and slower metabolism (Dempsey et al. 2004; Johnstone et al. 2006; Malaiyandi et al. 2006). At present, use of the nicotine metabolite ratio may be more preferable to assessing CYP2A6 genotype, given the large number of CYP2A6 alleles and the presence of non-genetic influences on nicotine metabolism rates (Ray et al. 2009).
