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Diabetes, lower extremity amputation, loss of protective sensation, and neuronal nitric oxide synthase associated protein in the C hronic R enal I nsufficiency C ohort study
Author(s) -
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
Publication year - 2012
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2012.00866.x
Subject(s) - medicine , diabetes mellitus , cohort , single nucleotide polymorphism , nitric oxide synthase , diabetic foot , endocrinology , nitric oxide , genotype , gene , genetics , biology
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 ( NOS1AP ) is associated with LEA and diabetic peripheral neuropathy ( DPN ). Our work used data from the C hronic R enal I nsufficiency C ohort ( 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, NOS1AP single nucleotide polymorphism rs1963645 was most strongly associated with LEA (1.73 [1.23, 2.44]). In A frican A mericans three NOS1AP 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 S emmes– W einstein 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 NOS1AP gene variants are associated with DPN and LEA .