Diabetes, lower extremity amputation, loss of protective sensation, and neuronal nitric oxide synthase associated protein in the Chronic Renal Insufficiency Cohort study. Issue 1 (10th December 2012)

• Record Type: Journal Article
• Authors: Margolis, David J.; Gupta, Jayanta; Thom, Stephen R.; Townsend, Raymond R.; Kanetsky, Peter A.; Hoffstad, Ole; Papdopoulos, Maryte; Fischer, Michael; Schelling, Jeffrey R.; Mitra, Nandita
• Is Part Of: Wound repair and regeneration. Volume 21:Issue 1(2013)
• Page Start: 17
• Page End: 24
• Publication Date: 2012-12-10
• Subjects: Wound healing -- Periodicals; Regeneration (Biology) -- Periodicals; 617.14
• DOI: 10.1111/j.1524-475X.2012.00866.x
• Languages: English
• ISSNs: 1067-1927

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Lower extremity amputation (LEA) is a life‐altering complication of diabetes. The goal of our study was to investigate the possibility that genetic variation in neuronal nitric oxide synthase associated protein <italic>(</italic>NOS1AP<italic>)</italic> is associated with LEA and diabetic peripheral neuropathy (DPN). Our work used data from the Chronic Renal Insufficiency Cohort (CRIC) study. CRIC is a multicenter investigation undertaken to pursue the relationship between chronic renal insufficiency and cardiovascular disease. We evaluated 3, 040 CRIC study subjects; 1, 490 individuals were African Americans and 1, 550 were whites. LEA occurred in 162 (5.3%) subjects, 93 (6.2%) of African Americans and 69 (4.4%) of whites. In whites, <italic>NOS1AP</italic> single nucleotide polymorphism rs1963645 was most strongly associated with LEA (1.73 [1.23, 2.44]). In African Americans three <italic>NOS1AP</italic> single nucleotide polymorphisms were associated with LEA: rs6659759 (1.65 [1.21, 2.24]); rs16849113 (1.58 [1.16, 2.14]); rs880296 (1.54 [1.14, 2.10]). We tested a subset of 100 CRIC participants for DPN using Semmes–Weinstein filaments. DPN in those with diabetes was associated with rs1963645 (16.97 [2.38, 120.97]) in whites and rs16849113 and rs6659759 (3.62 [1.11, 11.83] and 3.02 [0.82, 11.12], respectively) in African Americans. In conclusion, this is one of the first studies to show that <italic>NOS1AP</italic> gene variants are associated with DPN and LEA.</p> </abstract>