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

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $513,501

## Abstract

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.

## Key facts

- **NIH application ID:** 10149296
- **Project number:** 5R01DK116199-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** David Joel Margolis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $513,501
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149296

## Citation

> US National Institutes of Health, RePORTER application 10149296, NOS1AP and Capon Associated Impaired Healing in Those with Diabetic Foot Ulcers (5R01DK116199-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10149296. Licensed CC0.

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