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

近年来，日本肝细胞癌（HCC）的发病率显著上升。HCC患者在发病背景上多伴有丙型肝炎（HCV）相关慢性肝炎和肝硬化。在日本，66% - 94%的HCC患者抗hcv阳性和乙型肝炎病毒表面抗原（HBs）阴性，相比之下，在美国，HCC患者中抗hcv阳性的发生率明显较低，40%的HCC患者抗hcv阳性和乙型肝炎病毒表面抗原（HBs）阴性。这些结果表明存在物种差异（多态性）。由于环境致癌物在一定程度上影响肝细胞畸形（HCC）的发生过程，包括致癌物在内的各种外源物质（日本人和白种人）代谢能力的差异可能推断出两国之间HCC发生率的差异。我们采用基因分型的方法将与P450亚型CYP2C19相关的药物代谢能力分为广泛代谢者和不良代谢者。药物基因型方法利用PCR-RFLP方法筛选外显子4和外显子5，与药理表型有很好的对应关系。我们对30例HCV(+) HCC患者的基因型调查显示，30%的患者CYP2C19代谢不良，70%的患者CYP2C19代谢丰富。HCC的结果与健康的日本人的结果基本相似，此外，这些患者的特征及其在广泛代谢和低代谢之间的临床病程在临床环境中没有差异。

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.