Endothelial nitric oxide synthase (eNOS) variants were previously demonstrated in cardiovascular disease. To evaluate whether eNOS gene variants are associated with insulin resistance and type 2 diabetes, we evaluated polymorphisms in Exon7 (E298D), intron 18 (IVS18 + 27A-->C), and intron 23 (IVS23 + 10G-->T) in 159 type 2 diabetic patients without macrovascular complications and in 207 healthy control subjects. Samples for all hormonal and metabolic variables were obtained after an overnight fast. The D298 and IVS18 + 27C alleles, but not the IVS23 + 10G-->T variant, were significantly more frequent in type 2 diabetic patients than in control subjects. The two- and three-loci haplotype analysis showed that there is a statistically significant association between the eNOS variants and type 2 diabetes. No significant differences were observed in the clinical characteristics of type 2 diabetic patients according to genotypes (except for visceral obesity [waist-to-hip ratio], which was significantly more present in D298 homozygotes). Healthy control subjects homozygous for both D298 and IVS18 + 27C presented higher insulin, C-peptide, and nitric oxide levels, as well as higher HOMA (homeostasis model assessment) values than the double wild-type homozygotes, with values superimposable on those found in type 2 diabetic patients. In conclusion, we described a significant association between eNOS gene polymorphisms and type 2 diabetes, suggesting a new genetic susceptibility factor for hyperinsulinemia, insulin resistance, and type 2 diabetes.
Endothelial nitric oxide synthase polymorphisms are associated with type 2 diabetes and the insulin resistance syndrome / L.D. Monti, C. Barlassina, L. Citterio, E. Galluccio, C. Berzuini, E. Setola, G. Valsecchi, P. Lucotti, G. Pozza, L. Bernardinelli, G. Casari, P. Piatti. - In: DIABETES. - ISSN 0012-1797. - 52:5(2003 May), pp. 1270-1275.
|Titolo:||Endothelial nitric oxide synthase polymorphisms are associated with type 2 diabetes and the insulin resistance syndrome|
BARLASSINA, MARIA CRISTINA (Secondo)
|Parole Chiave:||genetic variation ; reference values ; nitric oxide synthase Type III ; nitric oxide synthase ; exons ; polymorphism, genetic ; humans ; diabetes Mellitus, Type 2 ; Introns ; cardiovascular diseases ; insulin resistance ; diabetic angiopathies|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||mag-2003|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.2337/diabetes.52.5.1270|
|Appare nelle tipologie:||01 - Articolo su periodico|