ArticleMalaria journal2015
Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania.
Article in Malaria journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it.Immunological reviews · 2020Review
- Association of EPCR Polymorphism rs867186-GG With Severity of Human Malaria.Frontiers in genetics · 2020Article
- Natural and Vaccine-Induced Acquisition of Cross-Reactive IgG-Inhibiting ICAM-1-Specific Binding of a Plasmodium falciparum PfEMP1 Subtype Associated Specifically with Cerebral Malaria.Infection and immunity · 2018Article
- Plasma Ang2 and ADAM17 levels are elevated during clinical malaria; Ang2 level correlates with severity and expression of EPCR-binding PfEMP1.Scientific reports · 2016Article
- The endothelial protein C receptor rs867186-GG genotype is associated with increased soluble EPCR and could mediate protection against severe malaria.Scientific reports · 2016Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEndothelial protein C receptor (EPCR) was recently identified as a key receptor for Plasmodium falciparum erythrocyte membrane protein 1 mediating sequestration of P. falciparum-infected erythrocytes in patients suffering from severe malaria. Soluble EPCR (sEPCR) inhibits binding of P. falciparum to EPCR in vitro and increased levels of sEPCR have been associated with the H3 haplotype of the EPCR encoding PROCR gene. It has been hypothesized that elevated sEPCR levels, possibly linked to the PROCR H3 genetic variant, may confer protection against severe forms of malaria. This study determined the frequencies of PROCR haplotypes H1-4 and plasma levels of sEPCR in a Tanzanian study population to investigate a possible association with severe malaria.
methodsStudy participants were children under 5 years of age admitted at the Korogwe District Hospital (N = 143), and diagnosed as having severe malaria (N = 52; including cerebral malaria N = 17), uncomplicated malaria (N = 24), or an infection other than malaria (N = 67). In addition, blood samples from 71 children living in nearby villages were included. The SNPs defining the haplotypes of PROCR gene were determined by post-PCR ligation detection reaction-fluorescent microsphere assay.
resultsIndividuals carrying at least one H3 allele had significantly higher levels of sEPCR than individuals with no H3 alleles (P < 0.001). No difference in the frequency of H3 was found between the non-malaria patients, malaria patients or the village population (P > 0.1). Plasma levels of sEPCR differed between these three groups, with higher sEPCR levels in the village population compared to the hospitalized patients (P < 0.001) and higher levels in malaria patients compared to non-malaria patients (P = 0.001). However, no differences were found in the distribution of H3 (P = 0.2) or levels of sEPCR (P = 0.8) between patients diagnosed with severe and uncomplicated malaria.
conclusionFrequencies of SNPs determining PROCR haplotypes were in concordance with other African studies. The PROCR H3 allele was associated with higher levels of sEPCR, confirming earlier findings, however, in this Tanzanian population; neither PROCR haplotype nor level of sEPCR was associated with severe malaria, however, larger studies are needed to confirm these findings.
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