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Immunogenetic analysis of pathogenesis of Chagas Disease in South America.

南美洲恰加斯病发病机制的免疫遗传学分析。

基本信息

批准号：
15406016
负责人：
HIRAYAMA Kenji
金额：
$ 8.51万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

1. Genetic analysis of pathogenisity of Trypanosoma cruzi in BoliviaPurpose : To identify any pathogenic strain of T.cruzi causing cardiopathy and or megacolon in the chronic Chagas Disease.Results : Collection of the blood samples from three different clinical groups, indeterminate, cardiac, and megacolon at three clinics and hospitals in Santa Cruz, Bolivia. DNA extracted from 10m1 peripheral blood was prepared from those samples. About 60% of the seropositive patients showed positive PCR reactions using genomic ribosomal RNA genes and Kinetoplast minicircle genes. All the identified parasite genes were clearly shown to be the lineage IId that had already reported. Using Minicircle DN A polymorphism, more sublineages were identified within our samples. But there was no co-relation between the sublineages and their pathogenicity.Discussion : Although it was successful to amplify the DNA fragments in the peripheral blood samples, there was no typical sublineages specifically provoke ca … More rdiac Chagas or megacolon Chagas. Further study will be needed to analyse their pathogenic differences, however, it is highly possible that host genetic factors are more influential to predict clinical prognosis of Chagas disease.2. Immunogenetic analysis of host genetic factors determining their clinical forms of chronic Chagas in Bolivia.Purpose : To identify host genetic factors that can predict the patients clinical prognosis in chronic Chagas.Results : We have collected 60 patients with Indeterminate, 71 pts with cardiac Chagas, and 72 patients with megacolon and got DNA from the blood samples. HLA-DRB1 alleles were determined from those samples and the frequencies of each allele were compε red between the groups. So far, there was no significant association between any DRB1 alleles and the clinical types.Discussion : Previous study in Guatemala showed an association between cardiac Chagas and HLA-B35, and MICA5 that are belonging to class I genes. The negative association was reproducible in those two studies using HLA-DRB1. We are now analyzing HLA-class I genes, HLA-A, B and MICA. It will be interesting if there are any reproducible association between class I gene alleles and cardiac. Less

1.玻利维亚克鲁斯锥虫致病性的遗传分析目的：鉴定慢性恰加斯病中引起心脏病和/或巨结肠的克鲁兹锥虫致病株。结果：在玻利维亚圣克鲁斯的三家诊所和医院采集了三种不同临床类型的血液样本：不明原因组、心脏组和巨结肠组。从10m1外周血中提取DNA。约60%的血清阳性患者使用基因组核糖体RNA基因和动粒体微环基因进行聚合酶链式反应。所有已鉴定的寄生虫基因都清楚地表明是已经报道的谱系IID。利用小环状DNA A多态性，在我们的样本中发现了更多的亚系。结论：虽然成功地从外周血标本中扩增出了…片段，但尚无典型的亚系特异性地诱发CA-DNA更多的Rdiac Chagas或巨型Chagas。但宿主遗传因素对恰加斯病的临床预后有较大影响的可能性较大，有待进一步研究。免疫遗传学分析决定玻利维亚慢性恰加病临床表现的宿主遗传因素。目的：确定可预测慢性CHAGA患者临床预后的宿主遗传因素。结果：收集60例不明原因患者、71例心脏恰加病患者和72例巨结肠患者，并从血样中提取DNA。从这些样本中检测到等位基因，各等位基因的频率组间比较ε红。到目前为止，尚未发现任何DRB1等位基因与临床类型有显著关联。讨论：危地马拉先前的研究表明，心脏CHAGA与属于I类基因的人类白细胞抗原B35和MICA5存在关联。在使用人类白细胞抗原-DRB1的这两项研究中，负相关性是可重现的。我们现在正在分析人类白细胞抗原-I类基因、人类白细胞抗原-A、B和MICA。如果在I类基因等位基因和心脏之间有任何可重复的关联，那将是很有趣的。较少