title: The A640G CYBA polymorphism associates with subclinical atherosclerosis in diabetes.
abstract: Oxidative stress is implicated in diabetes. The NADPH oxidases are the main source of superoxide in phagocytic and vascular cells, and p22phox is a key subunit. Genetic variants of CYBA, the human p22phox gene, associate with cardiovascular disease. We investigated the association of the A640G polymorphism with diabetes and its impact on phagocytic NADPH oxidase-dependent superoxide production and subclinical atherosclerosis. We studied 1212 subjects in which clinical parameters including carotid intima-media thickness (cIMT) were assessed. The A640G polymorphism was genotyped by TaqMan probes. In 496 subjects, the NADPH oxidase-dependent superoxide production in peripheral blood mononuclear cells was assessed by chemiluminescence. The GG genotype prevalence was significantly higher in type 2 diabetic patients than in non-diabetic subjects. Peripheral blood mononuclear cells from diabetic GG patients presented higher NADPH oxidase-dependent superoxide production than those of diabetic AA/AG patients. Within the diabetic group, GG patients presented higher cIMT levels than AA/AG patients. The A640G CYBA polymorphism may be a marker of oxidative stress risk and may be indicative of subclinical atherosclerosis in type 2 diabetes.
authors.affiliation: Division of Cardiovascular Sciences, Center for Applied Medical Research, University of Navarra, Navarra, Spain. mumoreno@unav.es
authors.forename: Maria de Ujue
authors.initials: MU
authors.lastname: Moreno
authors.forename: Gorka
authors.initials: G
authors.lastname: San Jose
authors.forename: Ana
authors.initials: A
authors.lastname: Fortuno
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Miguel-Carrasco
authors.forename: Oscar
authors.initials: O
authors.lastname: Beloqui
authors.forename: Javier
authors.initials: J
authors.lastname: Diez
authors.forename: Guillermo
authors.initials: G
authors.lastname: Zalba
mesh_terms: D050197:Atherosclerosis / Q000150:complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: D019255:NADPH Oxidases; C086986:CYBA protein, human