Genotype analysis of the CYP2C19 gene in HCV-seropositive patients with cirrhosis and hepatocellular carcinoma.
This study was conducted to assess whether the genotypic frequency of Smephenytoin 4'-hydroxylase CYP2C19 gene differs in Japanese cirrhotic patients who developed hepatocellular carcinoma. Thirty-eight patients with cirrhosis were studied. The wild-type allele CYP2C19*1 and the two mutated alleles, CYP2C19*2 and CYP2C19*3, were identified by PCR-RFLP method. Individuals with homozygous CYP2C19*2 or CYP2C19*3 mutation and those with CYP2C19*2 and CYP2C19*3 heterozygous mutation were predicted to be the poor metabolizer (PM) phenotype. The overall frequency of PM predicted from the genotyping analysis was 29% (11 of the 38 patients), consisting of 5 patients homozygous for CYP2C19*2, two homozygous for CYP2C19*3 and four heterozygous for the two defects. Among 24 HCV-seropositive patients with cirrhosis and hepatocellular carcinoma, the frequency of PM was 41.7% and significantly higher than that observed in 186 healthy controls. We postulate that the PM phenotype caused by the mutation of CYP2C19 gene in cirrhotic patients with HCV infection is associated with a high risk for developing hepatocellular carcinoma.
Chau
T K
TK
Department of Internal Medicine, Daisan Hospital, Jikei University School of Medicine, Komae, Tokyo, Japan.
Marakami
S
S
Kawai
B
B
Nasu
K
K
Kubota
T
T
Ohnishi
A
A
D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D016174:Hepacivirus; D006526:Hepatitis C / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19