Abstract
BackgroundCerebral malaria (CM) is characterized by the sequestration of Plasmodium-infected erythrocytes (pRBCs) to host brain microvasculature beds via P. falciparum erythrocyte membrane protein 1 (PfEMP1). Under normal conditions, activated protein C (APC) bound to endothelial protein C receptor (EPCR) has cytoprotective properties via the activation of protease-activated receptor 1 (PAR1). During malaria infection, pRBCs transports PfEMP1 to the membranes to bind EPCR in the same region as APC. As a result, APC is less capable of inducing cytoprotective effects via PAR1. Two studies involving adult malaria patients revealed that EPCR rs867186-GG allele is associated with protection against severe malaria, while three other studies involving child malaria patients could not show association between EPCR rs867186-GG genotype and severe malaria or increased mortality among children with CM.MethodsWe examined the association between the EPCR rs867186-GG genotype and the protection against cerebral malaria. Peripheral blood samples were collected from 47 malaria patients and 34 healthy individuals from a study conducted from 2004 to 2007 at the NSCB Medical College Hospital in India. CM and malaria-associated complications were defined based on WHO criteria. Genomic DNA was isolated from the peripheral blood mononuclear cells. Primer sequences were designed to contain rs867186 of the PROCR gene (NM 006404) and were used to amplify a 660 bp product as described before. PCR products were purified, and DNA sequences were determined by Sanger Sequencing (Genewiz, NJ). Nonparametric tests were used to compare the groups. To analyze differences in allele frequencies, we used chi-squared or Fisher's exact tests for categorical variables if the expected values were less than 5. P-value <0.05 was considered statistically significant.ResultsOur results showed significantly higher rates of AG and GG genotypes in CM patients compared to mild malaria (P = 0.0034). ConclusionOur results indicate that rs867186-GG or rs867186-AG genotypes are not associated with protection against HCM.
Highlights
Cerebral malaria (CM) is characterized by the sequestration of Plasmodium-infected erythrocytes to host brain microvasculature beds via P. falciparum erythrocyte membrane protein 1 (PfEMP1)
Our results showed significantly higher rates of AG and GG genotypes in CM patients compared to mild malaria (P = 0.0034)
Our results indicate that rs867186-GG or rs867186-AG genotypes are not associated with protection against HCM
Summary
Cerebral malaria (CM) is characterized by the sequestration of Plasmodium-infected erythrocytes (pRBCs) to host brain microvasculature beds via P. falciparum erythrocyte membrane protein 1 (PfEMP1). Cerebral malaria (CM) is characterized by the sequestration of parasitized red blood cells (pRBC) to host brain microvasculature beds via P. falciparum erythrocyte membrane protein 1 (PfEMP1) (Nielsen et al, 2002; Jensen et al, 2004; Bull et al, 2005; Kyriacou et al, 2006; Rottmann et al, 2006; Moxon et al, 2011; Lavstsen et al, 2012). Two studies involving African and Thai adult malaria patients revealed that EPCR rs867186-GG genotype is associated with protection against severe malaria (Naka et al, 2014; Shabani et al, 2016), while three other studies (Schuldt et al, 2014; Hansson et al, 2015; Moussiliou et al, 2015) involving African child malaria patients showed that EPCR gene GG variants are not associated with severe malaria or increased mortality among children with CM. We examined whether or not the EPCR rs867186-GG genotype is associated with protection against cerebral malaria in Indian malaria patients
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