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Genetic analysis in children with Escherichia coli O157-associated hemolytic uremic syndrome

大肠杆菌O157相关溶血性尿毒症综合征患儿的基因分析

基本信息

批准号：
15590855
负责人：
YOSHIKAWA Norishige
金额：
$ 2.24万
依托单位：
Wakayama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590855/
关键词：
Verotoxin (VT)-producing hemorrhagic colitis hemolytic uremic syndrome

项目摘要

Hemolytic uremic syndrome(HUS) is a significant cause of acute renal failure in children. Verotoxin(VT)-producing Escherichia coli(E.coli)(VTEC), particularly those of serogroup O157:H7, are the major cause of hemorrhagic colitis and are responsible for most cases of HUS. E.coli O157 produce large amounts of VT, which traverses polarized gastrointestinal epithelial cells, and gains the systemic circulation. It acts in initiating damage to target organs, such as kidney. Recently, a number of polymorphisms in human immunoregulatory genes have been reported Both the tumor necrosis factor-□(TNF-□) and interleukin-1□(IL-1□) gene loci contain polymorphisms that are associated with the increased secretion of TNF-□ and IL-1□^^〜__・ We therefore postulated that immunoregulatory gene polymorphisms might have an important role in the pathogenesis of HUS. To test this hypothesis, we investigated the effect of (1)TNF-□ promoter, (2)TNF-□, (3)IL-1□, (4)IL-1 receptor antagonist(IL-1RA) and (5)IL-1 typ … More e 1 receptor promoter(IL-1RI) gene polymorphisms on the incidence and the severity of Japanese children with VTEC associated HUS. We studied 48 consecutive Japanese pediatric patients with VTEC-associated HUS from eight hospitals in Japan. A total of 78 unrelated Japanese adult healthy volunteers were also studied as controls. Analysis of the genotype and allele frequencies of the five immunoregulatory genes was performed in the patients with VTEC-associated HUS and the control population. There were no significant differences in genotype and allele between patients with VTEC-associated HUS and healthy controls. There were no significant differences in age at onset, maximum blood urea nitrogen, maximum serum creatinine, duration of oligoanuria, ratio of patients requiring dialysis, minimum hemoglobin, minimum platelet count and ratio of patients with seizure among each genotype. In conclusion, we have demonstrated no efffect of immunoregulatory gene polymorphisms on the incidence and the severity of Japanese children with VTEC associated HUS. Less

溶血性尿毒症综合征（HUS）是儿童急性肾功能衰竭的重要原因。产生维罗毒素 (VT) 的大肠杆菌 (E.coli)(VTEC)，尤其是 O157:H7 血清群的大肠杆菌，是出血性结肠炎的主要原因，也是大多数 HUS 病例的病因。大肠杆菌O157产生大量的VT，穿过极化的胃肠道上皮细胞，并进入体循环。它会对目标器官（例如肾脏）造成损害。近年来，报道了多种人类免疫调节基因的多态性。肿瘤坏死因子-□(TNF-□)和白细胞介素-1□(IL-1□)基因位点均含有与TNF-□和IL-1的分泌增加相关的多态性□^^〜__・因此，我们推测免疫调节基因的多态性可能与TNF-□和IL-1的分泌增加有关。在 HUS 的发病机制中起重要作用。为了检验这一假设，我们研究了(1)TNF-□启动子、(2)TNF-□、(3)IL-1□、(4)IL-1受体拮抗剂(IL-1RA)和(5)IL-1典型e 1受体启动子(IL-1RI)基因多态性对日本儿童VTEC相关HUS的发病率和严重程度的影响。我们连续研究了来自日本 8 家医院的 48 名患有 VTEC 相关 HUS 的日本儿科患者。总共 78 名无关的日本成年健康志愿者也作为对照进行了研究。对 VTEC 相关 HUS 患者和对照人群的 5 个免疫调节基因的基因型和等位基因频率进行了分析。 VTEC 相关 HUS 患者与健康对照之间的基因型和等位基因没有显着差异。各基因型的发病年龄、最高血尿素氮、最高血清肌酐、少尿持续时间、需要透析的患者比例、最低血红蛋白、最低血小板计数和癫痫发作患者比例无显着差异。总之，我们证明免疫调节基因多态性对日本儿童 VTEC 相关 HUS 的发病率和严重程度没有影响。较少的