THE STUDY ON CYP2A6 GENETIC POLYMORPHISM

CYP2A6 is known as an enzyme responsible for the metabolism of coumarin. As its toxicological significance, aflatoxin B1 and NNK are metabolically activated by this CYP to mutagens. In our recent studies, we found that a newly developed drug, SM-12502, was a specific substrate of CYP2A6, and 3 out of 28 Japanese were poor metabolizers (PM) of this drug. Genomic analysis of CYP2A6 gene in the PM indicated that an existence of a new CYP2A6 gene variant which lacks the entire region of open reading frame for the enzyme. The frequency of the individual who possess the mutation homozygously was estimated as 3-4% in Japanese. During the course of investigation of the frequency, we found an another CYP2A6 variant whose 60 by region in the 3'-untranslated region was substituted by the corresponding sequences of CYP2A7 gene. In this study, we investigated the frequency of these polymorphic alleles as well as reported v1 (CYP2A6*2) variant among different race.