PLoS ONE (Jan 2021)

Role of ADAMTS13, VWF and F8 genes in deep vein thrombosis.

  • Maria Teresa Pagliari,
  • Andrea Cairo,
  • Marco Boscarino,
  • Ilaria Mancini,
  • Emanuela Pappalardo,
  • Paolo Bucciarelli,
  • Ida Martinelli,
  • Frits R Rosendaal,
  • Flora Peyvandi

DOI
https://doi.org/10.1371/journal.pone.0258675
Journal volume & issue
Vol. 16, no. 10
p. e0258675

Abstract

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BackgroundWe previously described the association between rare ADAMTS13 single nucleotide variants (SNVs) and deep vein thrombosis (DVT). Moreover, DVT patients with at least one rare ADAMTS13 SNV had a lower ADAMTS13 activity than non-carriers.AimsTo confirm ADAMTS13 variants association with DVT and reduced plasma ADAMTS13 activity levels in a larger population. To investigate the role of VWF and F8 variants.MethodsADAMTS13, VWF and F8 were sequenced using next-generation sequencing in 594 Italian DVT patients and 571 controls. Genetic association testing was performed using logistic regression and gene-based tests. The association between rare ADAMTS13 variants and the respective plasmatic activity, available for 365 cases and 292 controls, was determined using linear regression. All analyses were age-, sex- adjusted.ResultsWe identified 48 low-frequency/common and 272 rare variants. Nine low-frequency/common variants had a PConclusionsADAMTS13 and VWF low-frequency/common variants mainly showed a protective effect, although their association with DVT was not confirmed. DVT patients carrying a rare ADAMTS13 variants had slightly reduced ADAMTS13 activity levels, but a higher DVT risk. Rare VWF and FVIII variants were not associated with DVT suggesting that other mechanisms are responsible for the high VWF and FVIII levels measured in DVT patients.