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因严重疟疾而住院的儿童与 ICAM-1Kilifi 等位基因有关,但与恶性疟原虫感染的红细胞对 ICAM-1 的黏附模式无关。

Child hospitalization due to severe malaria is associated with the ICAM-1Kilifi allele but not adherence patterns of Plasmodium falciparum infected red blood cells to ICAM-1.

机构信息

Department of Immunology and Molecular Biology, Faculty of Medicine, Kilimanjaro Christian Medical College, Tumaini University, Tanzania.

出版信息

Acta Trop. 2010 Oct;116(1):45-50. doi: 10.1016/j.actatropica.2010.05.006. Epub 2010 May 27.

Abstract

This study aimed at determining whether the predisposition of a mutation at position 179 of the ICAM-1 gene to child hospitalization due to malaria was mediated by changes in adherence properties of IRBCs to ICAM-1. ICAM-1 genotypes were determined by nested polymerase chain reaction of isolated DNA from filter blood spots followed by Restriction Fragment Length Polymorphism (RFLP). Plasmodium falciparum adherence assays were done on immobilized purified ICAM-1. Our data indicate that the homozygosity for the ICAM-1(Kilifi) mutation occurs at a frequency of 22.3% in Magugu-Babati, Northern Tanzania. Our results show that there are no differences in IRBC binding profiles across genotypes. We show in this study that homozygosity for the ICAM-1(Kilifi) is associated with child hospitalization (X(2)=14.47, p<0.001). We have further shown that hospitalization was not associated with cytoadherence (X(2)=0.17, p=0.68). We conclude that the ICAM-1(Kilifi) allele occurs at a high frequency in Tanzania and that associations of this allele with higher child hospitalization frequencies is independent of cytoadherence patterns of IRBC isolated from ICAM-1 genotypes, implying that any associations reported to exist between the ICAM-1(Kilifi) mutation and severe malaria are unlikely to be mediated through altered IRBC cytoadherence properties.

摘要

本研究旨在确定 ICAM-1 基因 179 位突变是否易导致儿童因疟疾住院,其机制是否与 IRBC 对 ICAM-1 的黏附特性改变有关。通过从滤过血斑中分离的 DNA 进行巢式聚合酶链反应(PCR),随后进行限制性片段长度多态性(RFLP)分析,确定 ICAM-1 基因型。在固定化纯化的 ICAM-1 上进行恶性疟原虫黏附试验。我们的数据表明,在坦桑尼亚北部的 Magugu-Babati,ICAM-1(Kilifi)突变的纯合子频率为 22.3%。我们的结果表明,各基因型的 IRBC 结合特征没有差异。本研究表明,ICAM-1(Kilifi)纯合子与儿童住院(X(2)=14.47,p<0.001)有关。我们还表明,住院与细胞黏附无关(X(2)=0.17,p=0.68)。我们的结论是,ICAM-1(Kilifi)等位基因在坦桑尼亚的频率很高,该等位基因与较高的儿童住院频率相关,与从 ICAM-1 基因型中分离的 IRBC 的细胞黏附模式无关,这意味着报告的 ICAM-1(Kilifi)突变与严重疟疾之间存在的任何关联不太可能通过改变 IRBC 细胞黏附特性来介导。

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