title: Endothelial protein C receptor gene variants not associated with severe malaria in ghanaian children.
abstract: BACKGROUND
  Two recent reports have identified the Endothelial Protein C Receptor (EPCR) as a key molecule implicated in severe malaria pathology. First, it was shown that EPCR in the human microvasculature mediates sequestration of Plasmodium falciparum-infected erythrocytes. Second, microvascular thrombosis, one of the major processes causing cerebral malaria, was linked to a reduction in EPCR expression in cerebral endothelial layers. It was speculated that genetic variation affecting EPCR functionality could influence susceptibility to severe malaria phenotypes, rendering PROCR, the gene encoding EPCR, a promising candidate for an association study.
  
  
  METHODS
  Here, we performed an association study including high-resolution variant discovery of rare and frequent genetic variants in the PROCR gene. The study group, which previously has proven to be a valuable tool for studying the genetics of malaria, comprised 1,905 severe malaria cases aged 1-156 months and 1,866 apparently healthy children aged 2-161 months from the Ashanti Region in Ghana, West Africa, where malaria is highly endemic. Association of genetic variation with severe malaria phenotypes was examined on the basis of single variants, reconstructed haplotypes, and rare variant analyses.
  
  
  RESULTS
  A total of 41 genetic variants were detected in regulatory and coding regions of PROCR, 17 of which were previously unknown genetic variants. In association tests, none of the single variants, haplotypes or rare variants showed evidence for an association with severe malaria, cerebral malaria, or severe malaria anemia.
  
  
  CONCLUSIONS
  Here we present the first analysis of genetic variation in the PROCR gene in the context of severe malaria in African subjects and show that genetic variation in the PROCR gene in our study population does not influence susceptibility to major severe malaria phenotypes.
authors.affiliation: Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schuldt
authors.affiliation: Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Ehmen
authors.affiliation: Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Evans
authors.affiliation: Infectious Disease Epidemiology Group, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: May
authors.affiliation: School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ansong
authors.affiliation: Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Sievertsen
authors.affiliation: Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Muntau
authors.affiliation: Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Ruge
authors.affiliation: School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Tsiri
authors.initials: T
authors.lastname: Agbenyega
authors.affiliation: Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Horstmann
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D000074283:Endothelial Protein C Receptor; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D060005:Genotyping Techniques; D005869:Ghana; D006239:Haplotypes; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D016778:Malaria, Falciparum / Q000235:genetics*; D010641:Phenotype; D010963:Plasmodium falciparum / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011956:Receptors, Cell Surface