title: Novel mutations in the cytochrome P450 2C19 gene: a pitfall of the PCR-RFLP method for identifying a common mutation.
abstract: CYP2C19 is a clinically important enzyme involved in the metabolism of therapeutic drugs such as (S)-mephenytoin, omeprazole, proguanil, and diazepam. Individuals can be characterized as either extensive metabolizers (EM) or poor metabolizers (PM) on the basis of CYP2C19 enzyme activity. The PM phenotype occurs in 2-5% of Caucasian populations, but at higher frequencies (18-23%) in Asians. CYP2C19*2 and CYP2C19*3, which are single-nucleotide polymorphisms of CYP2C19, are the main cause of PM phenotyping in homozygotes or compound heterozygotes. We report two novel mutations in the CYP2C19 gene identified by direct sequencing and subcloning procedures. One of these mutations was considered to be CYP2C19*3 by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). This result suggests that mutations classed as CYP2C19*3 might include other mutations. Further studies are needed to clarify the relationship between these novel mutations and enzyme activity.
authors.affiliation: Department of Pediatrics, Neonatology and Congenital Disorders, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ohkubo
authors.affiliation: Department of Pediatrics, Neonatology and Congenital Disorders, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. a-ueta@med.nagoya-cu.ac.jp.
authors.forename: Akihito
authors.initials: A
authors.lastname: Ueta
authors.affiliation: Department of Pediatrics, Neonatology and Congenital Disorders, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ando
authors.affiliation: Department of Pediatrics, Neonatology and Congenital Disorders, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Pediatrics, Neonatology and Congenital Disorders, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Pediatrics, Neonatology and Congenital Disorders, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Kantaro
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Department of Pediatrics, Neonatology and Congenital Disorders, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sumi
authors.affiliation: Department of Hospital Pharmacy, Nagoya City University Hospital, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8602, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Laboratory of Hospital Pharmaceutics, Faculty of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Daiju
authors.initials: D
authors.lastname: Yamazaki
authors.affiliation: Laboratory of Hospital Pharmaceutics, Faculty of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Yukihisa
authors.initials: Y
authors.lastname: Kurono
authors.affiliation: Department of Pediatrics, Neonatology and Congenital Disorders, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.|Laboratory Medicine, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Fujimoto
authors.affiliation: Department of Pediatrics, Neonatology and Congenital Disorders, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Togari
mesh_terms: D000328:Adult; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D003001:Cloning, Molecular; D065731:Cytochrome P-450 CYP2C19; D017931:DNA Primers; D006580:Genetic Carrier Screening; D006801:Humans; D006899:Mixed Function Oxygenases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D015183:Restriction Mapping / Q000379:methods*; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19