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New insight into the hypercoagulability of Cushing's syndrome

Viviana Daidone1, Marco Boscaro, Elena Pontara

  • 1Department of Cardiologic, Thoracic and Vascular Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy.

Neuroendocrinology
|February 10, 2011
PubMed

Insights

Genetic variations in the von Willebrand factor (VWF) gene promoter, specifically haplotype 1 and short GT repeats, predict increased VWF levels and prothrombotic risk in Cushing's syndrome (CS). These findings offer new markers for assessing CS patients' risk.

Area of Science:

  • Endocrinology
  • Genetics
  • Thrombosis

Background:

  • Cushing's syndrome (CS) is associated with hypercoagulability and thromboembolic complications, primarily due to cortisol-induced increases in von Willebrand factor (VWF) and factor VIII.
  • This effect is linked to specific single nucleotide polymorphism (SNP) haplotypes in the VWF gene promoter, with haplotype 1 posing a higher risk for VWF upregulation than haplotype 2.
  • In healthy individuals, these SNPs correlate with VWF promoter polymorphisms: haplotype 1 with short (GT)n repeats (GTs) and haplotype 2 with long (GT)n repeats (GT(L)).

Purpose of the Study:

  • To precisely define the cortisol-sensitive VWF promoter pattern in Cushing's syndrome patients.
  • To investigate the association between VWF promoter polymorphisms, including SNP haplotypes and (GT)n locus variations, and VWF levels in CS.
  • To identify genetic markers for predicting VWF upregulation and prothrombotic risk in CS.

Main Methods:

  • Analysis of the (GT)n locus and SNP haplotypes in the VWF gene promoter.
  • Stratification of 80 Cushing's syndrome patients into two groups based on VWF levels: Group A (increased VWF) and Group B (normal VWF).
  • Statistical comparison of haplotype and (GT)n repeat frequencies between the groups.

Main Results:

  • Haplotype 1 and short (GT)n repeats (GTs) were significantly more frequent in CS patients with increased VWF (Group A).
  • Haplotype 1 and GTs conferred a 9-fold and 7.5-fold increased risk, respectively, for developing high VWF levels.
  • Haplotype 2 and long (GT)n repeats (GT(L)) were more prevalent in CS patients with normal VWF (Group B).
  • A higher prevalence of recombinant SNP haplotypes was observed in CS patients (6.2%) compared to healthy individuals (0.9%, p = 0.002).

Conclusions:

  • VWF promoter polymorphisms, specifically haplotype 1 and GTs, can predict cortisol-induced increases in VWF levels.
  • These genetic markers serve as novel indicators for assessing the prothrombotic risk associated with Cushing's syndrome.
  • Further research is needed to elucidate the clinical implications of the increased recombination rate of SNP haplotypes in the VWF promoter in CS.
Abstract

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