Genetic polymorphisms of vein wall remodeling in chronic venous disease: a narrative and systematic review

Blood. 2014 Aug 21;124(8):1242-50. doi: 10.1182/blood-2014-03-558478. Epub 2014 Jul 8.

Abstract

Chronic venous disease encompasses a spectrum of disorders caused by an abnormal venous system. They include chronic venous insufficiency, varicose veins, lipodermatosclerosis, postthrombotic syndrome, and venous ulceration. Some evidence suggests a genetic predisposition to chronic venous disease from gene polymorphisms associated mainly with vein wall remodeling. The literature exploring these polymorphisms has not been reviewed and compiled thus far. In this narrative and systematic review, we present the current evidence available on the role of polymorphisms in genes involved in vein wall remodeling and other pathways as contributors to chronic venous disease. We searched the EMBASE, Medline, and PubMed databases from inception to 2013 for basic science or clinical studies relating to genetic associations in chronic venous disease and obtained 38 relevant studies for this review. Important candidate genes/proteins include the matrix metalloproteinases (extracellular matrix degradation), vascular endothelial growth factors (angiogenesis and vessel wall integrity), FOXC2 (vascular development), hemochromatosis (involved in venous ulceration and iron absorption), and various types of collagen (contributors to vein wall strength). The data on associations between these genes/proteins and the postthrombotic syndrome are limited and additional studies are required. These associations might have future prognostic and therapeutic implications.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Chronic Disease
  • Collagenases / genetics
  • Collagenases / metabolism
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Genetic Predisposition to Disease*
  • Humans
  • Polymorphism, Genetic*
  • Postthrombotic Syndrome / genetics*
  • Postthrombotic Syndrome / metabolism
  • Postthrombotic Syndrome / pathology
  • PubMed
  • Varicose Ulcer / genetics*
  • Varicose Ulcer / metabolism
  • Varicose Ulcer / pathology
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Forkhead Transcription Factors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • mesenchyme fork head 1 protein
  • Collagenases