An Association Between Haemochromatosis Genotypes and Venous Leg Ulcers in Australian Individuals

Chronic venous disease underlies the pathogenicity of venous leg ulcers. However, it is unknown why some people with chronic venous disease are more susceptible to the development of venous leg ulcers (VLUs) than others. While there is evidence of a genetic component, our understanding of how specific genetic variants influence the development of chronic wounds and more specifically (VLUs) is limited. The aim of this study was to determine if specific genetic variants associated with the iron overload disorder haemochromatosis, HFE p.C282Y and HFE p.H63D, predispose to the development of VLUs. A total of 78 individuals with VLUs were genotyped for HFE variants and results compared to the HFE variant and genotype frequencies found in three different Australian population-based studies. The allele frequency of the HFE p.C282Y variant was 12.8% among individuals with a VLU, significantly higher than the frequencies of this variant reported in the three Australian population-based studies. The combined frequency of all genotypes containing the p.C282Y variant (HH/CY, HD/CY and HH/YY) was also significantly higher among individuals with a VLU compared to the control populations. The analysis of Australian individuals with VLUs indicates that the HFE p.C282Y variant is a genetic risk factor for the development of VLUs, suggesting that altered iron regulation may be a contributing factor to VLU pathogenesis.