Genetic polymorphisms in human Cyp2a6 gene and interindividual differences in nicotine metabolism

We determined the phenotyping of in vivo nicotine metabolism and the genotyping of the CYP2A6 gene in 92 Japanese and 209 Koreans. Among them, 3 Japanese and 4 Korean subjects who were absolutely deficient in cotinine formation were genotyped as CYP2A6*4 (whole deletion)/CYP2A6*4. The other poor metabolizers whose nicotine metabolism was impaired were genotyped as CYP2A6*4/CYP2A6*7 (I471T) or CYP2A6*4/CYP2A6*10 (I471T, R485L). The cotinine/nicotine ratio as an index of nicotine metabolism could be put in the order of subjects genotyped as CYP2A6*1A/CYP2A6*1A > CYP2A6*1A/ CYP2A6*9 (T-48G) > CYP2A6*9/CYP2A6*9. Thus, nicotine metabolism was impaired by CYP2A6*4, CYP2A6*7, and CYP2A6*10 alleles and was decreased by CYP2A6*9 allele.