Due to the slow rate of elimination, cotinine and its metabolite 3HC are useful in assessing nicotine exposure and metabolism. The ratio of 3HC to cotinine has been found to be a reliable marker for CYP2A6 activity and for individual differences in the rate of nicotine metabolism (Dempsey et al. 2004). Metabolism is faster in woman than in men, and reduced metabolism is found more frequently among Asians and African-Americans than among Caucasians and Hispanics (Benowitz et al. 2006a). Rate of nicotine metabolism has been associated with genetic polymorphisms in CYP2A6 (Benowitz et al. 2006b; Bloom et al. 2011; Malaiyandi et al. 2005; Mwenifumbo and Tyndale 2007); however, twin studies suggest that known CYP2A6 variants account for only a portion of the heritability of nicotine clearance rates (Ray et al. 2009; Swan et al. 2005).
