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1998 Fiscal Year Final Research Report Summary

Genetic polymorphism in the cytochrome P450-2C19 genes in Japanese patients with hepatocellu-lar carcinoma and hepatitis C infection

Research Project

Project/Area Number 08670629
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionDept.Int.Med., Daisan Hosp., Jikei University School of Medicine, Tokyo

Principal Investigator

OHNISHI Akihiro  Dept.Int.Med., Daisan Hosp., Jikei Univ., Instructor, 医学部, 講師 (00194225)

Co-Investigator(Kenkyū-buntansha) OSAKA Kazuhiro  Dept.Int.Med., Daisan Hosp., Jikei Univ., faculty, 医学部, 助手 (30246384)
MURAKAMI Shigeto  Dept.Int.Med., Daisan Hosp., Jikei Univ., 医学部, 講師 (20219893)
Project Period (FY) 1996 – 1998
Keywordspolymorphism / liver cirrhosis / chronic Ctype virus hepatitis / detoxication / P450 / hepatocellular carcinoma / genotype
Research Abstract

Recently there is a remarkable increase in population of hepatocellular carcinoma (HCC) in Japan. Most of the HCC patients have hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis on their background disease condition. In Japan 66 to 94 percent in HCC patients are anti-HCV positive as well as negative hepatitis B virus surface (HBs) antigen, in contrast in United State there is markedly low frequency in HCC patients with positive anti-HCV and forty percent in HCC patients are anti-HCV positive and negative hepatitis B virus surface (HBs) antigen. These results indicate the presence of species difference (polymorphism). Since environmental carcinogen partly affect the process of hepatocyte malformation (HCC), the difference in metabolizing capability of various xenobitics including carcinogen (Japanese vs. Caucacian) may extrapolate such difference in HCC frequency between two countries. We analyzed and divided the drug metabolizing capability related P450 subtype CYP2C19 using genotyping into extensive and poor metabolizer. Pharmacogenotype method screening exon 4 and exon 5, using PCR-RFLP mehtod, has been reported to be well corresponding with pharmacological phenotype. Our genotype survey in 30 HCC patients with HCV(+) revealed 30% in poor metabolizer and 70% in extensive metabolizer in CYP2C19. This result in HCC was mostly similar to those in healthy Japanese, in addition such patients characteristics and their clinical course between extensive and poor metabolizer did not differ in clinical settings.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Murakami S, et al.: "Hepatic denervation ameliorates sodium and water retention in experimental cirrhosis in rats" Dig Dis Sci. 42. 2292-2298 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagai N, et al.: "Pharmacokinetics and polymorphic oxidation of dextro-methorphan in a Japanese population" Biopharm Drug Disposi. 17. 421-433 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohnishi A, et al.: "Prostaglandin production in cirrhosis and portal hypertension - experimental and clinical study" Hepatology Res. 131-141 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohnishi A, et al.: "Careers in clinical pharmacology : present status and future academic perspectives in Japan" Trends Pharmacol Sci. 17. 45-47 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Reginald F Frye, et al.: "Validation of the five-drug “Pittsburgh cocktail" approach for assessment of selective regulation of drug-metabolizing enzymes" Clin Pharmacol Ther. 62. 365-376 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nasu K, et al.: "Genetic analysis of CYP2C9 polymorphism in a Japanese population" Pharmacogenetics. 7. 405-409 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohnishi A,Ishizaki T.: "Careers in clinical pharmacology : present status and future academic perspectives in Japan." Trends Pharmacol Sci. 17. 45-47 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagai N,Kawakubo T,Kaneko F,Ishii M,Shinohara R,Saito Y,Ohnishi A et al.: "Pharmacokinetics and polymorphic oxidation of dextromethorphan in a Japanese population." Biopharm Drug Disposi. 17. 421-433 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murakami S,Ohnishi A,Matsuo A,Kawai B,Tada Y,Kunihiro N,et al.: "Hepatic denervation ameliorates sodium and water retention in Experimental cirrhosis in rats." Digest Dis Sci. 42. 2292-2298 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohnishi A,Harada M,Matsuo A,Kawai B,Kunihiro N,Tanaka T,et al.: "Prostasglandin production in cirrhosis and portal hypertension-experimental and clinical study." Hepatology Res.10. 131-141 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Reeginald FF,Matzke GR,Adedoyin A,et al.: "Validation of the five-drug "Pittsburgh cocktail" approach for assessment of selective regulation of drug-metabolizing enzymes." Clin Pharmacol Ther. 62. 365-376 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nasu K,Kubota T,Ishizaki T.: "Genetic analysis of CYP2C9 polymorphism in a Japanese population." Pharmacogenetics. 7. 405-409 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chau T,Nasu K,Koguchi K,Ohnishi A.: "Genetic polymorphism in the cytochrome P450-2C19 genes in Japanese patients with hepatocellu-lar carcinoma and hepatitis C infection" Clin Pharmacol Ther. (submitted.). (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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