Association Between Nicotine Metabolism and CYP2A6*1 and CYP2A6*4 Genotypes in an Iranian Population

The cytochrome P450 (CYP) family is the principal enzyme system involved in the metabolism of xenobiotics and endogenous compounds. Among this family, CYP2A6 is one of the most important enzymes for metabolism of nicotine. In this study, the linkage of CYP2A6*1 and CYP2A6*4 genotypes with nicotine metabolism was investigated. A single polymerase chain reaction-restriction fragment length polymorphism was used to resolve the genotypes into CYP2A6*1 (wild type), CYP2A6*2, or CYP2A6*3. The population studied consisted of 200 healthy smokers from Mashhad city, North East of Iran. The urinary cotinine as the principal metabolite of nicotine was analyzed for 12 subjects (7 subjects with CYP2A6*1 as controls and 5 subjects with CYP2A6*4). The results indicated that cumulative urinary cotinine excretion in CYP2A6*4 genotype was about one-eighth compared with the control group (wild type). Cotinine formation from nicotine has individual and ethnic variability that correlated with the level of CYP2A6 expression. Moreover, urinary cotinine level was drastically lower in CYP2A6*4 subjects than in CYP2A6*1 subjects.