title: Reduced ADAMTS13 activity is associated with an ADAMTS13 SNP, fever and microparticles in a malaria-like model.
abstract: BACKGROUND
  Severe falciparum malaria (SM) remains a major cause of death in tropical countries. The reduced activity of ADAMTS13, increasing levels of ultra-large von Willebrand factor (ULVWF) in SM patients, are assumed as factors that intensify disease severity. However, the reason why ADAMTS13 activity is reduced in SM remains unclear.
  
  
  OBJECTIVE
  To investigate whether rs4962153, febrile temperature, and microparticles, contribute to reduced ADAMTS13 activity.
  
  
  METHODS
  Genotypic association of rs4962153 with ADAMTS13 antigen and activity was examined in 362 healthy Thai participants. The collagen binding assay was used to study the effects of febrile temperature and microparticles on ADAMTS13 activity.
  
  
  RESULTS
  ADAMTS13 antigen and activity were decreased in participants with AA genotype, compared to AG and GG (antigen: p-value = 0.014, and < 0.001; activity: p-value = 0.036, and < 0.002, respectively). There was significantly reduced ADAMTS13 antigen in AG compared to GG (p-value = 0.013), but not in ADAMTS13 activity (p-value = 0.082). The number of rs4962153 A alleles correlated with the reduced level of antigen and activity (p-value <0.001 and p-value = 0.001, respectively). MPs showed an inhibitory effect on ADAMTS13 activity (p-value = 0.025). Finally, ADAMTS13 activity was decreased in a temperature and time-dependent manner. The interaction between these two factors was also observed (p-value <0.001).
  
  
  CONCLUSIONS
  These findings suggest that the A allele of rs4962153, MPs, and febrile temperature, contribute to reduce ADAMTS13 activity in plasma. These data are useful in malaria or other diseases with reduced ADAMTS13 activity.
authors.forename: Sirima
authors.initials: S
authors.lastname: Kraisin
authors.forename: Attakorn
authors.initials: A
authors.lastname: Palasuwan
authors.forename: Supaluk
authors.initials: S
authors.lastname: Popruk
authors.affiliation: Department of Clinical Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand. nantadao@gmail.com.
authors.forename: Duangdao
authors.initials: D
authors.lastname: Nantakomol
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000235:genetics*; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005334:Fever / Q000469:parasitology / Q000503:physiopathology*; D056726:Genetic Association Studies; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics* / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D013785:Thailand; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human