The effects of endothelial nitric oxide synthase gene polymorphisms on endothelial function and metabolic risk factors in healthy subjects: the significance of plasma adiponectin levels

Abstract

Objective: Genetic variants of the endothelial nitric oxide synthase (eNOS) gene, Glu298Asp and T-786C, have been reported to be associated with cardiovascular disease. Adiponectin is an adipocytederived plasma protein with insulin-sensitizing and vascular protective effects; its levels are typically low in metabolic syndrome. Therefore, eNOS gene polymorphisms may also be associated with specific metabolic profiles, including plasma adiponectin levels and atherogenic lipids. Methods: We evaluated the functional significance of eNOS gene Glu298Asp and T-786C polymorphisms on endothelial function and metabolic profiles in 101 healthy young men (mean age 30.3 years) before the progression of atherosclerotic lesions. Results: No linkage disequilibrium was found between the two genotypes. The Asp298 allele carriers of the eNOS gene presented significantly higher plasma low density lipoprotein (LDL) cholesterol, LDL particle size, malondialdehyde-modified LDL (MDA-LDL), and fasting insulin levels and lower plasma high density lipoprotein (HDL) cholesterol, apolipoprotein A-I levels, and endothelium-dependent vasodilation when compared with noncarriers. In spite of higher MDA-LDL levels, Asp298 carriers had significantly larger LDL particle size. By contrast, in C-786 allele carriers, systolic blood pressure was significantly higher, and plasma high-molecular-weight adiponectin levels and endotheliumdependent vasodilation were significantly lower than those in non-carriers. Conclusions: Although both eNOS polymorphisms induced endothelial dysfunction, the eNOS T-786C polymorphism may be associated with adiponectin levels, whereas the Glu298Asp polymorphism may be associated with atherogenic lipid levels.

Gene polymorphisms in patients with type 2 diabetes and diabetic nephropathy

“…We demonstrated the importance of the T/C eNOS polymorphism as a risk factor for metabolic syndrome (which includes also T2D). We have confirmed previously published association studies with insulin resistance [51,52], the features of metabolic syndrome [53] and with type 2 diabetes [54]. The genotypic frequency of the I/D ACE polymorphism was found to be significantly different between arterial hypertensive patients and patients without hypertension.…”

Association between 894G>T endothelial nitric oxide synthase gene polymorphisms and metabolic syndrome

“…These studies include two surveys performed in a Spanish population that found a positive association between NOS3 polymorphisms and MS (19,20), and an Italian population study that found an association with diabetes mellitus type II and insulin resistance (21). Additionally, a positive association between 894G>T polymorphism and MS has been shown in Chinese and Japanese populations (18,22).…”

Prevalência de dislipidemia em adultos de meia-idade com polimorfismo do gene NOS3 e baixa aptidão cardiorrespiratória

“…Além disso, um estudo mostrou aumento nas concentrações plasmá-ticas de LDL-colesterol, LDL-colesterol modificado por malondialdeído (MDA-LDL-C) e níveis de insulina em jejum em indivíduos polimórficos para a posição Glu298Asp do gene da NOS3. Esses autores verificaram também redução das concentrações de HDL-C, apoliproteína I, e consequente redução na vasodilatação dependente de endotélio (31). Assim, parece-nos que o elo comum entre dislipidemia e polimorfismo no gene da NOS3 esteja na posição Glu298Asp, onde o glutamato é substituído pelo aspartato na enzima eNOS, modificando sua atividade enzimática e/ou menor ativação por estímulos físicos, como o shear stress.…”