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
| Project/Area Number |
08670629
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Dept.Int.Med., Daisan Hosp., Jikei University School of Medicine, Tokyo |
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Principal Investigator |
OHNISHI Akihiro Dept.Int.Med., Daisan Hosp., Jikei Univ., Instructor, 医学部, 講師 (00194225)
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| 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)
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| Project Period (FY) |
1996 – 1998
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| Keywords | polymorphism / liver cirrhosis / chronic Ctype virus hepatitis / detoxication / P450 / hepatocellular carcinoma / genotype |
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| 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.
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