Evidence for a genetic role in varicose veins and chronic venous insufficiency

Phlebology. 2012 Oct;27(7):329-35. doi: 10.1258/phleb.2011.011030. Epub 2012 Feb 3.


There is a strong body of circumstantial evidence which implicates genetics in the aetiology and pathology of varicose veins and venous ulcer disease. The aim of this review is to consider the current knowledge of the genetic associations and the ways in which new genetic technologies may be applied to advancing our understanding of the cause and progression of these venous diseases. A number of publications have used a candidate gene approach to identify genes implicated in venous disease. Although these studies have opened up important new insights, there has been a general failure to replicate results in an independent cohort of patients. With our limited knowledge of the biological pathways involved in the pathogenesis of venous disease we are not in a strong position to formulate truly erudite a priori candidate gene hypothesis-directed studies. A genome-wide association study should therefore be considered to help further our understanding of the genetic basis of venous disease. Due to the large sample sizes required for discovery and validation, using the new generations of molecular technologies, it will be necessary to form collaborating groups in order to successfully advance the field of venous disease genetics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chronic Disease
  • Disease Progression
  • Forkhead Transcription Factors / genetics
  • Gene Expression Profiling
  • Genetic Predisposition to Disease
  • Genetics, Population
  • Genome-Wide Association Study
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Thrombomodulin / metabolism
  • Varicose Veins / genetics*
  • Venous Insufficiency / genetics*


  • Forkhead Transcription Factors
  • Thrombomodulin
  • mesenchyme fork head 1 protein
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)