Several reduced and null activity alleles of the CYP2A6 gene have been identified and shown to alter enzyme activity and in vivo nicotine metabolism (Fernandez-Salguero et al. 1995; Goodz and Tyndale 2002; Mwenifumbo et al. 2008; Mwenifumbo and Tyndale 2007). The CYP2A6*1 allele is the “normal” activity (wild-type) variant and CYP2A6*1B is an increased activity allele (faster nicotine clearance). The CYP2A6*2 and *4 alleles are null activity alleles, occurring in about 20% of Asians and 1% of Caucasians (Nakajama et al. 2006; Rao et al. 2000; Schoedel et al. 2004). The CYP2A6*9 and *12 are found more commonly in Caucasian populations, about 9% of Caucasians carry one or more of these alleles (Malaiyandi et al. 2005; Schoedel et al. 2004). These alleles have reduced activity (slower nicotine clearance) (Mwenifumbo et al. 2008; Mwenifumbo and Tyndale 2007; Ray et al. 2009).
