Improved Real-Time PCR Assay for Homogeneous Multiplex Genotyping of Four CYP2C9 Alleles with Hybridization Probes

[摘要] The human cytochrome P450 2C (CYP2C) subfamily consists of four members (CYP2C8, -9, -18, and -19), which share >82% amino acid identity (1). The enzyme CYP2C9 metabolizes ∼10% of therapeutically important drugs (e.g., phenytoin and warfarin). The gene CYP2C9 is very polymorphic, with >10 alleles resulting from coding single-nucleotide polymorphisms (SNPs) (2). CYP2C9*1 is the wild-type allele. Other well-characterized variant alleles produce proteins with lower enzymatic activities and hence give rise to poor metabolizers. Interestingly, given the known effect of CYP2C9 genotype on warfarin hypersensitivity, use of the CYP2C9 genotype to predict clinical events is still a subject of debate (3). Variant alleles include CYP2C9*2 (430C>T; Arg144Cys), * 3 (1075A>C; Ile359Leu), * 4 (1076T>C; Ile359Thr), and * 5 (1080C>G; Asp360Glu). To date, allele * 4 has been found only in one Japanese patient, whereas the other three alleles have been reported …

[学科分类] 过敏症与临床免疫学