C242TCYBAPolymorphism of the NADPH Oxidase Is Associated With Reduced Respiratory Burst in Human Neutrophils
- 1 June 2004
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 43 (6), 1246-1251
- https://doi.org/10.1161/01.hyp.0000126579.50711.62
Abstract
Oxidative stress contributes to the pathogenesis of atherosclerosis. p22phox-based NAD(P)H oxidases exist in the vessel wall, acting as important superoxide-generating systems in the vasculature. Some studies have identified reduced atherosclerosis in the presence of the C242T CYBA polymorphism, whereas others have not. Because vascular p22phox is identical to neutrophil p22phox, we studied the association between the C242T, A640G, and −930A/GCYBA polymorphisms and the quantity of superoxide produced from neutrophils isolated from healthy adults to determine if these polymorphisms had any functional impact on NADPH oxidase function. Neutrophils were isolated from 90 subjects by Percoll density gradient centrifugation. Genotypes were determined by polymerase chain reaction (PCR) and restriction mapping, as well as real-time PCR. The oxidative burst was stimulated with phorbol 12-myristate 13-acetate. Superoxide was quantified using the superoxide dismutase inhibitable oxidation of the spin probe hydroxylamine 1-hydroxy-3-carboxy-pyrrolidine, detected by electron paramagnetic resonance. Superoxide production was significantly affected by the C242T polymorphism, being 8.7±0.7, 7.9±0.6, and 5.9±1.2 μmol/L per minute per 106 neutrophils for the C242T CC, CT, and TT genotypes, respectively (PA/G polymorphisms did not alter the neutrophil respiratory burst. Phagocytic respiratory burst activity in homozygous individuals with the T allele of the C242T CYBA polymorphism is significantly lower than of wild-type carriers and heterozygous individuals. Because p22phox exists in both the neutrophil and vessel wall, vascular oxidative stress is likely diminished in individuals with this polymorphism.Keywords
This publication has 23 references indexed in Scilit:
- Preliminary characterisation of the promoter of the human p22phox gene: identification of a new polymorphism associated with hypertensionFEBS Letters, 2003
- The A640G and C242T p22phoxPolymorphisms in Patients with Coronary Artery DiseaseAntioxidants and Redox Signaling, 2002
- Identification of a Spectrally Stable Proteolytic Fragment of Human Neutrophil Flavocytochrome b Composed of the NH2-terminal Regions of gp91 and p22Published by Elsevier BV ,2001
- The p22 phox polymorphism C242T is not associated with CHD risk in Asian Indians and ChineseEuropean Journal of Clinical Investigation, 1999
- NADH/NADPH oxidase p22phox C242T polymorphism and coronary artery disease in the Australian populationEuropean Journal of Clinical Investigation, 1999
- Spin Trapping of Superoxide Radicals and Peroxynitrite by 1-Hydroxy-3-carboxy-pyrrolidine and 1-Hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine and the Stability of Corresponding Nitroxyl Radicals Towards Biological ReductantsBiochemical and Biophysical Research Communications, 1997
- Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability.JCI Insight, 1996
- Neutrophils obtained from obliterative atherosclerotic patients exhibit enhanced resting respiratory burst and increased degranulation in response to various stimuliBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1996
- Stoichiometry of p22-phox and gp91-phox in phagocyte cytochrome b558Biochemistry, 1995
- Individual Comparisons by Ranking MethodsJournal of Economic Entomology, 1945