Novel CYP2A6 diplotypes identified through next-generation sequencing are associated with in-vitro and in-vivo nicotine metabolism

Objective Smoking patterns and cessation rates vary widely across smokers and can be influenced by variation in rates of nicotine metabolism (i.e. cytochrome P450 2A6, CYP2A6, enzyme activity). There is high heritability of CYP2A6-mediated nicotine metabolism (60–80%) due to known and unidentified genetic variation in the CYP2A6 gene. We aimed to identify and characterize additional genetic variants at the CYP2A6 gene locus.