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Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania.

Hansson HH, Turner L, Møller L, Wang CW, Minja DT, Gesase S, Mmbando B, Bygbjerg IC, Theander TG, Lusingu JP, Alifrangis M, Lavstsen T - Malar. J. (2015)

Bottom Line: 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.Individuals carrying at least one H3 allele had significantly higher levels of sEPCR than individuals with no H3 alleles (P < 0.001).Frequencies of SNPs determining PROCR haplotypes were in concordance with other African studies.

View Article: PubMed Central - PubMed

Affiliation: Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Science, University of Copenhagen, Østerfarimagsgade 5, Building 22-23, 1356, Copenhagen K, Denmark. Hellehan@sund.ku.dk.

ABSTRACT

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.

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Related in: MedlinePlus

Soluble endothelial protein C receptor (sEPCR) levels in acute malaria patients and after follow-up. sEPCR levels were measured in acute ill malaria patients and after recovery (N = 28). The level of sEPCR was significantly lower (P = 0.001) during acute illness compared to the same patients after recovery. The significance level was set to P < 0.05
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Fig2: Soluble endothelial protein C receptor (sEPCR) levels in acute malaria patients and after follow-up. sEPCR levels were measured in acute ill malaria patients and after recovery (N = 28). The level of sEPCR was significantly lower (P = 0.001) during acute illness compared to the same patients after recovery. The significance level was set to P < 0.05

Mentions: Finally, to investigate if there was any difference in sEPCR level during malaria and 3 weeks post-treatment, a sub-set of 28 children was included in a follow-up study (Fig. 2). The level of sEPCR was significantly higher during convalescence [median 163.8 ng/ml, (25/75 quartiles = 126.7/280.1)], than during acute infection [median 138.3 ng/ml, (25/75 quartiles = 116.6/164.3)], P = 0.001.Fig. 2


Haplotypes of the endothelial protein C receptor (EPCR) gene are not associated with severe malaria in Tanzania.

Hansson HH, Turner L, Møller L, Wang CW, Minja DT, Gesase S, Mmbando B, Bygbjerg IC, Theander TG, Lusingu JP, Alifrangis M, Lavstsen T - Malar. J. (2015)

Soluble endothelial protein C receptor (sEPCR) levels in acute malaria patients and after follow-up. sEPCR levels were measured in acute ill malaria patients and after recovery (N = 28). The level of sEPCR was significantly lower (P = 0.001) during acute illness compared to the same patients after recovery. The significance level was set to P < 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666078&req=5

Fig2: Soluble endothelial protein C receptor (sEPCR) levels in acute malaria patients and after follow-up. sEPCR levels were measured in acute ill malaria patients and after recovery (N = 28). The level of sEPCR was significantly lower (P = 0.001) during acute illness compared to the same patients after recovery. The significance level was set to P < 0.05
Mentions: Finally, to investigate if there was any difference in sEPCR level during malaria and 3 weeks post-treatment, a sub-set of 28 children was included in a follow-up study (Fig. 2). The level of sEPCR was significantly higher during convalescence [median 163.8 ng/ml, (25/75 quartiles = 126.7/280.1)], than during acute infection [median 138.3 ng/ml, (25/75 quartiles = 116.6/164.3)], P = 0.001.Fig. 2

Bottom Line: 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.Individuals carrying at least one H3 allele had significantly higher levels of sEPCR than individuals with no H3 alleles (P < 0.001).Frequencies of SNPs determining PROCR haplotypes were in concordance with other African studies.

View Article: PubMed Central - PubMed

Affiliation: Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Science, University of Copenhagen, Østerfarimagsgade 5, Building 22-23, 1356, Copenhagen K, Denmark. Hellehan@sund.ku.dk.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus