The role of genetics in chronic venous disease and venous leg ulcers

Background
Chronic leg ulcers affect 1-3% of adults over 60 years and are considerably costly to treat with costs exceeding $3 billion. The majority of leg ulcers (60-70%) coincide with underlying structural damage in the veins of the affected leg, however, the exact cause of the ulceration remains unknown. It is well established that venous disease has a strong genetic association, yet, our understanding of this is limited. It has been found the gene variants associated with poor control of iron metabolism, which can occur with leaking veins, correlates with an increased risk of developing venous leg ulcers (VLUs). An online survey showed an 8% prevalence of VLUs among 151 HFE-C282Y homozygotes, considerably higher than the expected prevalence. For this reason haemochromatosis, which is the most common genetic disorders in Australia has been discussed as having a possible relationship with venous disease and/or VLUs.
Objective(s)
The objective of this study is to determine whether HFE mutations are more prevalent in patients with VLUs and hence may be involved in the pathogenesis of chronic venous disease.
Method
Clinical details will be obtained by questionnaire and review of clinical records. DNA will be extracted from blood samples and used to genotype patients for the two common HFE mutations, C282Y and H63D.
Results and Conclusions
Outcomes of this project will help to identify the genetic factors contributing to VLU pathogenesis and may uncover potential new mechanisms. Importantly the results will allow future molecular studies to further uncover the genetic determinants of VLU pathogenesis.