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Reduced ADAMTS13 activity is associated with an ADAMTS13 SNP, fever and microparticles in a malaria-like model

Sirima Kraisin, Attakorn Palasuwan, Supaluk Popruk

  • 1Department of Clinical Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand. nantadao@gmail.com.

Malaria Journal
|January 7, 2014
PubMed
Abstract

Insights

Reduced ADAMTS13 activity in severe malaria is linked to the rs4962153 A allele, microparticles (MPs), and febrile temperatures. These factors contribute to decreased ADAMTS13 levels, impacting disease severity.

Area of Science:

  • Hematology
  • Genetics
  • Infectious Diseases

Background:

  • Severe falciparum malaria (SM) is a significant cause of mortality in tropical regions.
  • Reduced ADAMTS13 activity and increased ultra-large von Willebrand factor (ULVWF) are implicated in SM severity.
  • The underlying causes of decreased ADAMTS13 activity in SM are not fully understood.

Purpose of the Study:

  • To investigate the contribution of the rs4962153 genetic variant, febrile temperature, and microparticles (MPs) to reduced ADAMTS13 activity.
  • To explore the relationship between these factors and ADAMTS13 levels in the context of malaria.

Main Methods:

  • Genotyping for rs4962153 and its association with ADAMTS13 antigen and activity in 362 healthy Thai participants.
  • In vitro collagen binding assays to assess the impact of febrile temperatures and MPs on ADAMTS13 activity.
  • Statistical analysis to determine correlations and interactions between genetic factors, environmental conditions, and ADAMTS13 function.

Main Results:

  • The AA genotype of rs4962153 was associated with significantly lower ADAMTS13 antigen and activity compared to AG and GG genotypes.
  • The presence of microparticles (MPs) demonstrated an inhibitory effect on ADAMTS13 activity.
  • ADAMTS13 activity decreased in a temperature- and time-dependent manner, with a significant interaction between these factors.

Conclusions:

  • The A allele of rs4962153, microparticles, and febrile temperatures are identified as contributors to reduced ADAMTS13 activity in plasma.
  • These findings provide insights into the mechanisms underlying ADAMTS13 dysfunction in malaria.
  • The data may be relevant for understanding and managing malaria and other diseases characterized by reduced ADAMTS13 activity.

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