ArticleMalaria journal2014
Association of the endothelial protein C receptor (PROCR) rs867186-G allele with protection from severe malaria.
Article in Malaria journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 28 citations in OpenAlex.
- Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant.Thrombosis and haemostasis · 2015Trial
- Genetic variants and serum biomarkers of CXCL8, MAP3K7, LTA/TNF, EXOC3L1, PROCR, and TRAF2 in Age-Related macular degeneration: associations with disease risk and therapeutic response.Scientific reports · 2026Article
- Bioinformatic analysis of rare endothelial protein C receptor missense variants associated with coagulation and thrombophilia risk.Scientific reports · 2025Article
- A Catalogue of Structural Variation across Ancestrally Diverse Asian Genomes.Nature communications · 2024Article
- Association of EPCR Polymorphism rs867186-GG With Severity of Human Malaria.Frontiers in genetics · 2020Article
- Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it.Immunological reviews · 2020Review
- Plasmodium falciparum infected erythrocytes can bind to host receptors integrins αVβ3 and αVβ6 through DBLδ1_D4 domain of PFL2665c PfEMP1 protein.Scientific reports · 2018Article
- 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
- Endothelial protein C receptor polymorphisms and risk of sepsis in a Chinese population.The Journal of international medical research · 2017Article
- Article
- The endothelial protein C receptor rs867186-GG genotype is associated with increased soluble EPCR and could mediate protection against severe malaria.Scientific reports · 2016Article
- Beninese children with cerebral malaria do not develop humoral immunity against the IT4-VAR19-DC8 PfEMP1 variant linked to EPCR and brain endothelial binding.Malaria journal · 2015Article
- Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania.Malaria journal · 2015Article
- Structural conservation despite huge sequence diversity allows EPCR binding by the PfEMP1 family implicated in severe childhood malaria.Cell host & microbe · 2015Article
- Review
- Endothelial protein C receptor gene variants not associated with severe malaria in ghanaian children.PloS one · 2014Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCytoadhesion of Plasmodium falciparum-infected erythrocytes to endothelial cells in microvessels is a remarkable characteristic of severe malaria. The endothelial protein C receptor (EPCR), encoded by the endothelial protein C receptor gene (PROCR), has recently been identified as an endothelial receptor for specific P. falciparum erythrocyte membrane protein 1 (PfEMP1) subtypes containing domain cassettes (DCs) 8 and 13. The PROCR rs867186-G allele (serine-to-glycine substitution at position 219 of EPCR; 219Gly) has been shown to be associated with higher levels of plasma soluble EPCR (sEPCR). In this study, the association of PROCR rs867186 with severe malaria is examined in Thai population.
methodsA total of 707 Thai patients with P. falciparum malaria (341 with severe malaria and 336 with mild malaria) were genotyped for rs867186. To assess the association of PROCR rs867186 with severe malaria, three models (dominant, recessive and allelic) were evaluated. The rates of non-synonymous and synonymous substitutions were estimated for the coding sequence of the PROCR gene.
resultsThe rs867186-GG genotype was significantly associated with protection from severe malaria (P-value=0.026; odds ratio=0.33; 95% confidence interval=0.12-0.90). Evolutionary analysis provided no evidence of strong positive selection acting on the PROCR gene.
conclusionThe rs867186-GG genotype showed significant association with protection from severe malaria. The present results suggest that PfEMP1-EPCR interaction, which can mediate cytoadhesion and/or reduce cytoprotective and anti-inflammatory effects, is crucial to the pathogenesis of severe malaria.
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