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Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania
BACKGROUND: Endothelial 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. f...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666078/ https://www.ncbi.nlm.nih.gov/pubmed/26620701 http://dx.doi.org/10.1186/s12936-015-1007-6 |
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author | Hansson, Helle Holm Turner, Louise Møller, Line Wang, Christian William Minja, Daniel T. R. Gesase, Samwel Mmbando, Bruno Bygbjerg, Ib Christian Theander, Thor G. Lusingu, John P. A. Alifrangis, Michael Lavstsen, Thomas |
author_facet | Hansson, Helle Holm Turner, Louise Møller, Line Wang, Christian William Minja, Daniel T. R. Gesase, Samwel Mmbando, Bruno Bygbjerg, Ib Christian Theander, Thor G. Lusingu, John P. A. Alifrangis, Michael Lavstsen, Thomas |
author_sort | Hansson, Helle Holm |
collection | PubMed |
description | BACKGROUND: Endothelial 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. METHODS: Study 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. RESULTS: Individuals 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. CONCLUSION: Frequencies 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. |
format | Online Article Text |
id | pubmed-4666078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46660782015-12-02 Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania Hansson, Helle Holm Turner, Louise Møller, Line Wang, Christian William Minja, Daniel T. R. Gesase, Samwel Mmbando, Bruno Bygbjerg, Ib Christian Theander, Thor G. Lusingu, John P. A. Alifrangis, Michael Lavstsen, Thomas Malar J Research BACKGROUND: Endothelial 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. METHODS: Study 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. RESULTS: Individuals 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. CONCLUSION: Frequencies 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. BioMed Central 2015-12-01 /pmc/articles/PMC4666078/ /pubmed/26620701 http://dx.doi.org/10.1186/s12936-015-1007-6 Text en © Hansson et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Hansson, Helle Holm Turner, Louise Møller, Line Wang, Christian William Minja, Daniel T. R. Gesase, Samwel Mmbando, Bruno Bygbjerg, Ib Christian Theander, Thor G. Lusingu, John P. A. Alifrangis, Michael Lavstsen, Thomas Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania |
title | Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania |
title_full | Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania |
title_fullStr | Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania |
title_full_unstemmed | Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania |
title_short | Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania |
title_sort | haplotypes of the endothelial protein c receptor (epcr) gene are not associated with severe malaria in tanzania |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666078/ https://www.ncbi.nlm.nih.gov/pubmed/26620701 http://dx.doi.org/10.1186/s12936-015-1007-6 |
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