CYP2C19活性および遺伝子変異と肝臓癌病態の関連

概要

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This study was conducted to assess whether the genotypec frequency of S-mephenytoin 4'-hydroxylase CYP2C19 is affected by hepatic carcinoma. Method: Liver samples were donated from Japanese hepatic cancer patients who received partial hepatectomy; fifteen had hepatocellular carcinoma (HCC) and 22 had metastatic hepatic cancer (MC) . Individual CYP2C19 genotypes were determined by PCR-based amplification method followed by restriction fragment length analysis. Hepatic microsomal CYP2C19 activity was determined by S-mephenytoin 4'-hydroxylation (S-MP 4'-OH) . A higher frequency of CYP2C19 gene mutation both in exon 4 and 5 was observed in MC patients compared to HCC patients. S-MP 4'-OH was relatively well correlated to the genotype in the samples from MC patients; most samples with CYP2C19 *1/*1 showed comparable activity to that of healthy subjects reported although the samples with mutations showed lower activity. In contrast, declined activity of the enzyme was observed in HCC samples in spite of the existence of mutations. These results suggest that low activity of CYP2C19 in MC patients was due to the enzyme deficiency caused by mutation of the CYP2C19 gene. In addition, a CYP2C19 deficiency might reflect the potentials of carcinoma metastasis of the liver.
学校法人昭和大学・昭和医学会の論文