TY - JOUR T1 - GENETIC POLYMORPHISMS OF CYP2C8 IN JAPANESE POPULATION JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 687 LP - 690 DO - 10.1124/dmd.31.6.687 VL - 31 IS - 6 AU - Miki Nakajima AU - Yuto Fujiki AU - Kumiko Noda AU - Hiroki Ohtsuka AU - Hisashi Ohkuni AU - Satoru Kyo AU - Masaki Inoue AU - Yukio Kuroiwa AU - Tsuyoshi Yokoi Y1 - 2003/06/01 UR - http://dmd.aspetjournals.org/content/31/6/687.abstract N2 - CYP2C8 plays important roles in metabolizing therapeutic drugs and endogenous compounds. Although genetic polymorphisms of CYP2C8 were reported, there is little information on CYP2C8 polymorphisms in the Japanese population. In the present study, we screened for previously described polymorphisms in the coding region of this gene using polymerase chain reaction (PCR)-restriction fragment length polymorphism or allele specific-PCR analyses. Eleven polymorphisms of CYP2C8*2 (I269F), CYP2C8*3 (R139K, K399R), CYP2C8*4 (I264M), CYP2C8*5 (frameshift), T130N, E154D, N193K, K249R, L390S, P404A, and H411L have been comprehensively investigated in at least 200 Japanese individuals. A single subject was heterozygous for CYP2C8*5, and the allele frequency was calculated as 0.0025. The other single nucleotide polymorphisms (SNPs) were not found in the Japanese subjects in the present study. Thus, it appears that the frequencies of these alleles in Japanese are extremely low. In addition, concerning the SNPs of T130N, E154D, N193K, K249R, and H411L, it remains clear that these alleles exist as polymorphisms or represent sequence errors or cloning artifacts. Although several SNPs such as CYP2C8*2, CYP2C8*3, CYP2C8*4, and P404A have been reported to reduce the enzymatic activity, pharmacokinetic abnormalities of drugs metabolized by polymorphic CYP2C8 might be rare in Japanese. The American Society for Pharmacology and Experimental Therapeutics ER -