Diabetes mellitus has reached epidemic proportions. A significant complication of diabetes is impaired healing which results in diabetic foot ulcer (DFU) and lower extremity amputation (LEA). About 20% of those with diabetes will develop a DFU. The annual incidence of LEA in Medicare beneficiaries with diabetes is about 4 per thousand, but rates of LEA can vary up to two- to threefold by race/ethnicity, geographic location, and gender. Individuals with diabetes develop DFU and LEA for many reasons that probably include interactions or alterations in intrinsic pathways responsible for wound repair, the presence of infection, changes to immune regulation, neuropathy, peripheral vascular disease, changes in anatomic function of the foot, and local trauma. DFUs are chronic wounds, which are by definition are wounds that have failed to follow an orderly and timely sequence resulting in healing and have impaired healing. Those that develop chronic wounds that result in LEA have wounds that heal slowly or not at all. Why a wound becomes chronic is not well understood. In the past 5 years, we have developed preliminary evidence showing that genetic variation in NOS1AP, which codes for a protein called capon, is associated with impaired healing of DFU, an increased risk of LEA, and decrease in the number or circulating endothelial precursors cells, which have been shown to be associated with individuals with a DFU that are less likely to heal. Our project focuses on producing further evidence to confirm the association of NOS1AP variation with impaired healing and to discern the functional basis of NOS1AP genetic variation on capon and ultimately capon?s influence on wound repair. To that end, the goal of our present study is to explore the possibility that common genetic variants of NOS1AP in those who have diabetes are associated with alterations in wound repair.
Diabetic foot ulcers are a significant complication of diabetes. For the first time we have compelling preliminary data that genetic variation is associated with an increased risk of this complication of diabetes. Our goal is to better understand this risk and to evaluate how genetic variation effects the ability to heal these wounds.