A novel single nucleotide polymorphism (SNP) of the CYP2C19 gene in a Japanese subject with lowered capacity of mephobarbital 4'-hydroxylation.
We sequenced all nine exons and exon-intron junctions of the cytochrome P450 2C19 (CYP2C19) gene from a Japanese subject with a lowered capacity of CYP2C19-mediated 4'-hydroxylation after an oral administration of mephobarbital. We found a novel single nucleotide polymorphism (SNP) of CYP2C19 gene as follows: SNP, 040110MoritaJ001; GENENAME: CYP2C19; ACCESSION NUMBER: NT_030059.8; LENGTH; 25 bases; 5'-GAGGGCCTGGCCC/TGCATGGAGCTGT-3'. The SNP (168946C>T) induced an amino acid alteration (Arg442Cys) located in exon 9 close to the heme-binding region of CYP2C19, which may result in the decrease in the catalytic properties of CYP2C19. A new allele having this SNP was designated as CYP2C19*16.
Morita
Jun
J
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Japan.
Kobayashi
Kaoru
K
Wanibuchi
Atsuko
A
Kimura
Miyuki
M
Irie
Shin
S
Ishizaki
Takashi
T
Chiba
Kan
K
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001120:Arginine / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000172:deficiency* / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D003545:Cysteine / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D004789:Enzyme Activation / Q000235:genetics; D006580:Genetic Carrier Screening; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008618:Mephobarbital / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000172:deficiency* / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D008618:Mephobarbital; D001120:Arginine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D003545:Cysteine