[Genetic polymorphism of the CYP2C subfamily].
Cytochromes P450 (CYP) are a superfamily of hemoproteins that metabolize various foreign compounds. The human CYP2C subfamily is one of the subfamilies of the CYP2 family and it consists of four members of CYP isoforms, CYP2C8, CYP2C9, CYP2C18 and CYP2C19. A well-characterized genetic polymorphism occurs in CYP2C19, which is associated with the 4'-hydroxylation of S-mephenytoin. There are two phenotypes, extensive metabolizers and poor metabolizers (PM) of mephenytoin. The frequency of PM in the Japanese population is 20%, while only 3% of Caucasians are PM of mephenytoin. Two defective alleles, designated as CYP2C19*2 and CYP2C19*3, have been described, and the latter mutation has been detected only in Oriental populations. Recently, an allelic variant of CYP2C9 that causes substitution of Leu359 for Ile359 has been shown to be associated with the decreased metabolic clearance of various therapeutic agents including warfarin, tolbutamide and phenytoin. The frequency of this variant allele in the Japanese population is 2%, while those of the Caucasians are 6-9%. Although the role of CYP2C18 in the drug metabolism remains obscure, we have recently found that defective alleles of CYP2C19*3 and CYP2C18m1 are completely linked, suggesting that PM of CYP2C19 with CYP2C19*3 alleles is a PM of CYP2C18 and vice versa.
Laboratory of Biochemical Pharmacology and Toxicology, Faculty of Pharmaecutical Sciences, Chiba University, Japan.
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Chiba
D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000502:physiology; D005006:Ethnicity / Q000235:genetics; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000502:physiology
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C082185:CYP2C18 protein, human; C045793:CYP2C19 protein, human; C450259:CYP2C8 protein, human; D065731:Cytochrome P-450 CYP2C19; D065727:Cytochrome P-450 CYP2C8; D039181:Steroid 16-alpha-Hydroxylase