NOS1AP and Capon Associated Impaired Healing in Those with Diabetic Foot Ulcers

项目摘要/摘要 糖尿病已经达到了流行的程度。糖尿病的一个重要并发症是受损 导致糖尿病足溃疡(DFU)和下肢截肢(LEA)的愈合。其中约20% 糖尿病患者会发展成DFU。在患有糖尿病的医疗保险受益人中，LEA的年发病率约为 千分之四，但LEA比率可能因种族/民族、地理位置和 性别。糖尿病患者发生DFU和LEA的原因有很多，可能包括相互作用或 负责伤口修复的内在通路的变化，感染的存在，免疫的变化 调节，神经病变，周围血管疾病，足部解剖功能的变化，以及局部 精神创伤。DFU是慢性伤口，根据定义，这些伤口没有遵循有序和 及时的顺序导致愈合，并且已经损害了愈合。那些形成慢性伤口的人会导致 在LEA，伤口愈合缓慢或根本不愈合。伤口为什么会变得慢性还不是很清楚。 在过去的5年里，我们发展了初步的证据表明NOS1AP的遗传变异， 编码一种名为Capon的蛋白质，与DFU的愈合受损，LEA风险增加， 以及循环内皮前体细胞的数量减少，这已被证明是 与不太可能痊愈的DFU患者相关。我们的项目专注于进一步生产 证实NOS1AP变异与受损的愈合相关的证据和辨别功能性 CAPON的NOS1AP基因变异基础及最终CAPON对伤口修复的影响。为此， 我们目前的研究目的是探索NOS1AP的常见遗传变异在这些患者中的可能性 患有糖尿病的人与伤口修复的变化有关。

Project Summary/Abstract 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.