title: Association of ADAMTS13 polymorphism with cerebral malaria.
abstract: BACKGROUND
  Cerebral malaria is one of the most severe manifestations of Plasmodium falciparum malaria. The sequestration of parasitized red blood cells (PRBCs) to brain microvascular endothelium has been shown to contribute to the pathophysiology of cerebral malaria. Recent studies reported increased levels of von Willebrand factor (VWF) and reduced activity of VWF-cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), in patients with cerebral malaria.
  
  
  METHODS
  Association of six single nucleotide polymorphisms (SNPs) of the ADAMTS13 gene with cerebral malaria was examined in 708 Thai patients with P. falciparum malaria.
  
  
  RESULTS
  Among six SNPs, the derived allele of a SNP located in intron 28, rs4962153-A, was significantly associated with protection against cerebral malaria when 115 cerebral malaria patients were compared with 367 mild malaria patients (Fisher's exact P-value = 0.0057; OR = 0.27; 95% CI = 0.096-0.76). Significant association was also detected between 115 cerebral malaria and 593 non-cerebral malaria (226 non-cerebral severe malaria and 367 mild malaria) patients (Fisher's exact P-value = 0.012; OR = 0.30; 95% CI = 0.11-0.83).
  
  
  CONCLUSIONS
  Excessive adhesion of PRBCs to the platelet-decorated ultra-large VWF (ULVWF) appears to enhance the sequestration of PRBCs to cerebral microvascular endothelium. The genetic association observed in the present study implies that the regulation of platelet-decorated ULVWF strings by ADAMTS13 may play a role in the development of cerebral malaria.
authors.affiliation: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Sirima
authors.initials: S
authors.lastname: Kraisin
authors.forename: Izumi
authors.initials: I
authors.lastname: Naka
authors.forename: Jintana
authors.initials: J
authors.lastname: Patarapotikul
authors.forename: Duangdao
authors.initials: D
authors.lastname: Nantakomol
authors.forename: Pornlada
authors.initials: P
authors.lastname: Nuchnoi
authors.forename: Hathairad
authors.initials: H
authors.lastname: Hananantachai
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D060467:Disease Resistance; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016779:Malaria, Cerebral / Q000235:genetics*; D016778:Malaria, Falciparum / Q000150:complications* / Q000235:genetics*; D010963:Plasmodium falciparum / Q000472:pathogenicity; D020641:Polymorphism, Single Nucleotide; D013785:Thailand; D055815:Young Adult
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human