Plasmodium falciparum malaria in south-west Nigerian children:: Is the polymorphism of ICAM-1 and E-selectin genes contributing to the clinical severity of malaria?
Plasmodium falciparum malaria in south-west Nigerian children:: Is the polymorphism of ICAM-1 and E-selectin genes contributing to the clinical severity of malaria?
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DOI：
10.1016/j.actatropica.2005.05.011
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发表时间：
2005-09-01
期刊：
影响因子：
2.7
通讯作者：
Omotade, OO
中科院分区：
文献类型：
--
作者：
Amodu, OK;Gbadegesin, RA;Omotade, OO
恶性疟原虫疟疾仍然是撒哈拉以南非洲儿童的主要公共卫生危害，虽然决定疟疾临床结果变化的因素尚未完全确定，但宿主和寄生虫因素以及它们之间复杂的分子相互作用都涉及其中。恶性疟原虫感染的红细胞的细胞粘附特性被认为是疟疾发病机制的关键特性，宿主粘附分子的多态性可能与疟疾的严重程度有关。从223名儿童中收集了临床信息和血液样本伊巴丹（尼日利亚西南部），中位年龄为34.5个月，表现出不同的疟疾临床无症状寄生虫病（ACP）临床表现，急性无并发症疟疾（UM）和严重疟疾（SM）-根据WHO标准定义。研究了4种人类粘附分子编码基因在6个不同位点（ICAM-1外显子2、4和6，E-选择素外显子2，CD 36外显子10和PECAM外显子3）的多态性。用PCR-RFLPs方法对上述6个外显子进行基因分型，其中ICAM-1第4外显子为单态。其余位点均处于Hardy-Weinberg平衡（HWE）。E-选择素基因座具有非常低的杂合性（类似于0.06），与所研究的其它基因座（0.23-0.44）形成对比。一旦对协变量（年龄和寄生虫密度）的数据进行进一步处理，并将ACP组作为参考类别，结果表明，在ICAM-1外显子6处存在G等位基因的情况下，严重疟疾的风险增加（3.6倍）。就E-选择素外显子中的T等位基因而言，UM和SM类别中带有T等位基因的DNA样本数量太少，无法在现阶段得出任何相关结论。总之，这些结果表明，宿主粘附分子位点的遗传多态性是严重疟疾易感性的一个重要变量。需要对宿主基因座进行进一步研究，以进一步确定哪些多态性与严重疟疾相关，并增加我们对宿主-寄生虫相互作用生物学的了解。(c)2005 Elsevier B. V.保留所有权利。
Plasmodium falciparum malaria remains a major public health hazard in sub- Saharan African children, While the factors that determine the variations in clinical outcome of a malaria have not been completely defined both host and parasite factors, as well as the complex molecular interactions between them have been implicated. The cyto-adherent properties of the P.falciparum-infected red blood cells are considered as key properties in the pathogenesis of malaria and the polymorphisms of the host adhesion molecules could contribute to the severity of malaria.Clinical information and blood samples were collected from 223 children from Ibadan (south-west Nigeria), median age of 34.5 months, presenting with different clinical manifestations of malaria-clinically asymptomatic parasitism (ACP), acute uncomplicated malaria (UM) and severe malaria (SM)-as defined by WHO criteria. The polymorphisms of genes coding for four human adhesion molecules at six different loci (ICAM-1 exons 2, 4 and 6, E-selectin exon 2, CD36 exon 10, and PECAM exon 3) were studied. DNA samples were prepared for further genotyping of the six exons mentioned above by PCR-RFLPs using the appropriate restriction digests for each loci.The ICAM-1 exon 4 locus was monomorphic. All the other loci were at Hardy-Weinberg equilibrium (HWE). The E-selectin locus had very low heterozygosity (similar to 0.06) in contrast to the other loci under study (0.23-0.44). Once the data was further processed for covariates (age and parasite density) and taking as the reference category the ACP group, results show that in the presence of the G allele at the (ICAM-1 exon 6 there is an increased risk (3.6 times) of severe malaria. As far as the T allele in the E-selectin exon is concerned, the number of sampled DNAs with the T allele within both the UM and SM categories is too low for drawing any relevant conclusion at this stage. In conclusion, these results suggest that genetic polymorphisms at host adhesion molecules loci are an important variable in the susceptibility to severe malaria. Further studies of host loci are needed to further delineate which polymorphisms are associated with severe malaria and increase our knowledge of the biology of host-parasite interactions. (c) 2005 Elsevier B.V. All rights reserved.