Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox subunit polymorphisms, systemic oxidative stress , endothelial dysfunction, and atherosclerosis in type 2 diabetes mellitus

INTRODUCTION Diabetes mellitus is an important and rapidly increasing problem in public health. It is associated with endothelial dysfunction and increased endothelial permeability, which may lead to severe cardiovascular events. OBJECTIVES We aimed to evaluate the relationship between polymorphisms of the cytochrome b-245 alpha chain (CYBA) gene encoding p22phox, a key subunit of nicotinamide adenine dinucleotide phosphate oxidase, and endothelial function, atherosclerosis, and systemic oxidative stress in type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS Intima-media thickness as well as flow-and nitroglycerin-mediated dilatation were measured in 182 patients with T2DM. Assessment of plasma levels of von Willebrand factor and malondialdehyde as well as genotyping of the coding sequence C242T (rs4673) and promoter region A-930G (rs9932581) polymorphisms of CYBA were performed using standardized protocols. RESULTS We observed a significant association of the impaired endothelial function, as measured by flow-mediated dilatation, with the C allele of the C242T polymorphism, but not with the A-930G polymorphism. Functional relationship of the C242T polymorphism with endothelial dysfunction remained significant following a multivariable adjustment for major risk factors for atherosclerosis. Mean intima-media thickness, nitroglycerin-mediated dilatation, and concentrations of malondialdehyde or von Willebrand factor were not related to the specific genotypes of the investigated polymorphisms. CONCLUSIONS The C242T polymorphism of the CYBA gene significantly affects endothelial function in T2DM, whereas the A-930G polymorphism does not. Thus, the former might be a useful marker of endothelial dysfunction in patients with T2DM.

Automated summary

The C242T polymorphism of the CYBA gene is significantly associated with endothelial dysfunction in patients with T2DM, making it a potentially useful marker for this condition.