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Study on possible correlation between carcinogenic risk and genetic variation of hepatitis B and C viruses in Indonesia.

印度尼西亚乙型和丙型肝炎病毒致癌风险与遗传变异之间可能相关性的研究。

基本信息

批准号：
16406015
负责人：
HOTTA Hak
金额：
$ 6.78万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

1. Analysis of hepatitis B virus (HBV) : All of HBV isolates obtained in Surabaya, Indonesia, were classified into genotype B on the basis of partial S region sequences of the HBV genome while they were classified into genotype C on the basis of preC/C region sequences of the HBV genome. These results strongly suggest the possibility that these Indonesian HBV strains emerged through genetic recombination between genotypes B and C. There are 32 nucleotide residues (4.5% of the entire preC/C region sequence) that appear to be typical for genotype C, among which 7 residues (corresponding to 6 amino acid residues ; 2.8% of the entire preC/C peptides) are non-synonymous mutations. This recombinant type of HBV between genotypes B and C was isolated from all types of disease status, such asymptomatic carrier, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Interestingly, HBV isolates obtained from patients with liver cirrhosis and hepatocellular carcinoma had a tendency to po … More ssess quasi-species sequences with a unique sequence at the carboxy-terminus that are rarely found in asymptomatic carriers and patients with chronic hepatitis.2. Analysis of hepatitis C virus (HCV) : On the basis of secondary structure of the amino-terminal 120 residues of the NS3 protein, a majority of HCV isolates obtained in Surabaya, Indonesia, were classified into subgroup B1-1, which were shown to be closely associated with the occurrence of hepatocellular carcinoma in Japanese patients. Moreover, unique subgroups of HCV, which were rarely found in Japan, were frequently isolated in Indonesia. Although statistical significance was not achieved due probably to the small number of samples tested, it was interesting that HCV strains of the B1-1 subgroup prevail in Indonesia, where HCV-associated hepatocellular carcinoma is pretty common. We also observed that a considerable number of HCV isolates obtained from patients with hepatocellular carcinoma possessed four or more mutations in the interferon sensitivity-determining region (ISDR) of the NS5A protein. This result implies the possible benefit of interferon treatment for patients with HCV-associated hepatocellular carcinoma. Less

1. B型肝炎病毒（HBV）的分析：根据HBV基因组的部分S区序列将所有从印度尼西亚泗水获得的HBV分离株分类为基因型B，而根据HBV基因组的前C/C区序列将它们分类为基因型C。这些结果强烈提示这些印度尼西亚HBV毒株通过基因型B和C之间的遗传重组而出现的可能性。有32个核苷酸残基（整个preC/C区序列的4.5%），似乎是典型的基因型C，其中7个残基（对应于6个氨基酸残基;整个preC/C肽的2.8%）是非同义突变。这种介于基因型B和C之间的重组型HBV分离自所有类型的疾病状态，如无症状携带者、慢性肝炎、肝硬化和肝细胞癌。有趣的是，从肝硬化和肝细胞癌患者中获得的HBV分离株有感染的倾向， ...更多信息 SSSS准种序列在羧基端具有独特的序列，在无症状携带者和慢性肝炎患者中很少发现。丙型肝炎病毒（HCV）的分析：根据NS 3蛋白氨基末端120个残基的二级结构，将在印度尼西亚泗水获得的大多数HCV分离株分为B1-1亚组，该亚组显示与日本患者肝细胞癌的发生密切相关。此外，在日本很少发现的独特的HCV亚群在印度尼西亚经常被分离出来。尽管可能由于检测的样本数量较少而未达到统计学显著性，但有趣的是，HCV B1-1亚群毒株在印度尼西亚流行，HCV相关肝细胞癌在印度尼西亚非常常见。我们还观察到，相当数量的HCV分离株获得的肝细胞癌患者具有四个或更多的突变的干扰素敏感性决定区（ISDR）的NS 5A蛋白。这一结果意味着干扰素治疗HCV相关肝细胞癌患者的可能益处。少