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Mendelian Randomization Analysis of Hemostatic Factors and Their Contribution to Peripheral Artery Disease-Brief

Aeron M Small1,2, Jennifer E Huffman3, Derek Klarin3,4,5

  • 1Corporal Michael J. Crescenz VA Medical Center, PA (A.M.S., K.-M.C., S.M.D.).

Arteriosclerosis, Thrombosis, and Vascular Biology
|August 28, 2020
PubMed

Insights

Genetic analysis reveals that factor VIII (FVIII) and von Willebrand factor (VWF) are linked to peripheral artery disease (PAD). This suggests a role for hemostasis and thrombosis in PAD development.

Area of Science:

  • Cardiovascular Genetics
  • Hemostasis and Thrombosis
  • Vascular Biology

Background:

  • Peripheral artery disease (PAD) is a common atherosclerotic disease linked to disability and mortality.
  • The role of hemostatic factors, beyond Factor V Leiden, in PAD is not well understood.
  • Genetic evidence suggests a potential link between procoagulation factors and PAD.

Purpose of the Study:

  • To investigate the role of key hemostatic factors in the development of PAD.
  • To utilize Mendelian randomization to assess the causal relationship between hemostatic factors and PAD.
  • To identify specific hemostatic factors associated with increased PAD risk.

Main Methods:

  • Two-sample Mendelian randomization analysis was employed.
  • Genome-wide association study (GWAS) summary statistics for hemostatic factors (FVII, FVIII, FXI, VWF, fibrinogen) and PAD were used.
  • The ABO locus was identified as a significant genetic instrument for FVIII and VWF.

Main Results:

  • Genetically determined factor VIII (FVIII) was significantly associated with PAD (OR, 1.41; P=6.0×10-7).
  • Genetically determined von Willebrand factor (VWF) was also significantly associated with PAD (OR, 1.28; P=0.0073).
  • No significant association was found for factors VII, XI, or fibrinogen with PAD.

Conclusions:

  • Hemostasis and thrombosis likely play a role in the pathophysiology of PAD.
  • Factor VIII and von Willebrand factor emerge as potential contributors to PAD.
  • Further research is needed to elucidate the independent biological roles of VWF and FVIII in PAD.
Abstract

Keywords:
coronary artery diseasefibrinogenodds ratioperipheral artery diseasevascular endothelium

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