Venous leg ulcers (VLU) are debilitating wounds that can remain unhealed for several decades and recur in up to 70% of cases. The progression and recalcitrance of the condition is not well understood and, although there is evidence to suggest a genetic predisposition, the genes involved have yet to be elucidated.
A suite of six candidate genes has been selected based on their proposed involvement with venous health. Using a genotyping approach these genes will be analyzed in VLU patients and age matched controls while the protein in patient wound fluid samples will be analyzed using quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS). The abundance of proteins associated with the target genes and related biochemical pathways will be a focus of this study, in addition to comparison of wound fluid biochemistry to VLU associated clinical parameters. Bioinformatic integration of genetic and proteomic datasets will be performed to determine if there is a genetic link to the biochemistry that underpins non-healing venous leg ulcers. This will be performed using gene ontology and pathway enrichment in applications such as Reactome, Ingenuity Pathway Analysis and Cytoscape. We hypothesise that the genomic analysis will demonstrate a differential expression of wildtype and variant genes between the control and patient cohorts for some or all of the six target genes. Moreover, it is expected that quantitative proteomics of ulcer fluid will show differential abundance in the protein profile between healing ulcers and recalcitrant wounds. In addition, it is anticipated that proteins associated with the target genes will have an altered abundance in non-healing or slow healing wounds. Finally, through integration of our datasets, we expect to find that patients with variant copies of genes will display clinical symptoms that correlate with the physiological role or pathway of the gene as measured at the protein level.