One genetic factor that plays an important role in the development of smoking behaviors is variation in the gene CYP2A6, which encodes the cytochrome P450 enzyme responsible for the majority of oxidation of nicotine to cotinine; this is the primary pathway of nicotine metabolism in humans (Hukkanen et al., 2005). The CYP2A6 locus is highly polymorphic, and alleles with reduced function have been associated with slower rates of nicotine metabolism. Common variants define multiple CYP2A6 haplotypes in individuals of European ancestry (Haberl et al., 2005), and the majority of inter-individual variation in the metabolism of nicotine to cotinine is explained by CYP2A6 genotypes in European Americans (Bloom et al., 2011).
