PMID- 33851807 OWN - NLM STAT- MEDLINE DCOM- 20210628 LR - 20220531 IS - 1897-9483 (Electronic) IS - 0032-3772 (Linking) VI - 131 IP - 5 DP - 2021 May 25 TI - Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox subunit polymorphisms, systemic oxidative stress, endothelial dysfunction, and atherosclerosis in type 2 diabetes mellitus. PG - 447-454 LID - 10.20452/pamw.15937 [doi] AB - INTRODUCTION: Diabetes mellitus is an important and rapidly increasing problem in public health. It associates with endothelial dysfunction and increased endothelial permeability, which may lead to severe cardiovascular events. OBJECTIVES: We aimed to evaluate the relationship between polymorphisms in the cytochrome b-245 alpha chain (CYBA) gene encoding p22phox, a key subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, with endothelial function, atherosclerosis and systemic oxidative stress in type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: Intima-media thickness (IMT), flow- and nitroglycerin-mediated dilatation (FMD and NMD) were measured in 182 patients with T2DM. Assessment of plasma levels of von Willebrand factor (vWF) and malondialdehyde (MDA) levels as well as genotyping of 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 FMD, with the C allele of C242T, 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 IMT, NMD, concentrations of MDA or vWF were not related to the specific genotypes of the investigated polymorphisms. CONCLUSIONS: C242T, but not A-930G, polymorphism of CYBA significantly affects endothelial function in T2DM. Thus, it might be a useful marker of endothelial dysfunction in T2DM patients. FAU - Osmenda, Grzegorz AU - Osmenda G AD - Department of Internal and Agricultural Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland FAU - Matusik, Pawel T AU - Matusik PT AD - Department of Internal and Agricultural Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland AD - Department of Electrocardiology, Institute of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland FAU - Sliwa, Tomasz AU - Sliwa T AD - Department of Internal and Agricultural Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland FAU - Czesnikiewicz-Guzik, Marta AU - Czesnikiewicz-Guzik M AD - Department of Periodontology and Oral Sciences Research Group, University of Glasgow Dental School and Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom AD - Department of Dental Prophylaxis and Experimental Dentistry, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland FAU - Skupien, Jan AU - Skupien J AD - Department of Metabolic Diseases, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland FAU - Malecki, Maciej T AU - Malecki MT AD - Department of Metabolic Diseases, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland FAU - Siedlinski, Mateusz AU - Siedlinski M AD - Department of Internal and Agricultural Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland. mateusz.siedlinski@uj.edu.pl LA - eng PT - Journal Article DEP - 20210414 PL - Poland TA - Pol Arch Intern Med JT - Polish archives of internal medicine JID - 101700960 RN - 53-59-8 (NADP) RN - EC 1.6.3.- (NADPH Oxidases) RN - EC 1.6.3.1 (CYBA protein, human) SB - IM MH - *Atherosclerosis/genetics MH - Carotid Intima-Media Thickness MH - *Diabetes Mellitus, Type 2/complications/genetics MH - Humans MH - NADP MH - NADPH Oxidases/genetics/metabolism MH - Oxidative Stress/genetics EDAT- 2021/04/15 06:00 MHDA- 2021/06/29 06:00 CRDT- 2021/04/14 09:12 PHST- 2021/04/15 06:00 [pubmed] PHST- 2021/06/29 06:00 [medline] PHST- 2021/04/14 09:12 [entrez] AID - 10.20452/pamw.15937 [doi] PST - ppublish SO - Pol Arch Intern Med. 2021 May 25;131(5):447-454. doi: 10.20452/pamw.15937. Epub 2021 Apr 14.