This Article Full Text Full Text (PDF) All Versions of this Article: 43/6/1246    most recent 01.HYP.0000126579.50711.62v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wyche, K. E. Articles by Zafari, A. M. Search for Related Content PubMed PubMed Citation Articles by Wyche, K. E. Articles by Zafari, A. M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB 12-O-TETRADECANOYLPHORBOL-13-ACETATE Related Collections Clinical genetics Risk Factors Cell biology/structural biology Genetics of cardiovascular disease Mechanism of atherosclerosis/growth factors

(Hypertension. 2004;43:1246.)
© 2004 American Heart Association, Inc.

Scientific Contributions

C242T CYBA Polymorphism of the NADPH Oxidase Is Associated With Reduced Respiratory Burst in Human Neutrophils

Keith E. Wyche; Shaoshan S. Wang; Kathy K. Griendling; Sergey I. Dikalov; Harland Austin; Swapna Rao; Bruno Fink; David G. Harrison; A. Maziar Zafari

From the Department of Medicine (K.E.W., S.S.W., K.K.G., S.I.D., S.R., B.F., D.G.H., A.M.Z.), Division of Cardiology, Emory University, Atlanta, Ga; Atlanta Veterans Affairs Medical Center (S.S.W., S.R., D.G.H., A.M.Z.), Decatur, Ga; and Rollins School of Public Health (H.A.), Department of Epidemiology, Emory University, Atlanta, Ga.

Correspondence to Dr A. Maziar Zafari, Emory University School of Medicine, Division of Cardiology, 1639 Pierce Drive, 319 WMB, Atlanta, GA 30322. E-mail azafari{at}emory.edu

Oxidative stress contributes to the pathogenesis of atherosclerosis. p22^phox-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 p22^phox is identical to neutrophil p22^phox, we studied the association between the C242T, A640G, and –930^A/G CYBA 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 (P<0.05). In contrast, the A640G and the –930^A/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 p22^phox exists in both the neutrophil and vessel wall, vascular oxidative stress is likely diminished in individuals with this polymorphism.

Key Words: atherosclerosis • neutrophils • oxidative stress • polymorphism • risk factors

This article has been cited by other articles:

				M. Arca, B. Conti, A. Montali, P. Pignatelli, F. Campagna, F. Barilla, G. Tanzilli, R. Verna, A. Vestri, C. Gaudio, et al. C242T Polymorphism of NADPH Oxidase p22phox and Recurrence of Cardiovascular Events in Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 752 - 757. [Abstract] [Full Text] [PDF]

				Hardev Ramandeep Singh Girn, S. Ahilathirunayagam, A. I. D. Mavor, and S. Homer-Vanniasinkam Reperfusion Syndrome: Cellular Mechanisms of Microvascular Dysfunction and Potential Therapeutic Strategies Vascular and Endovascular Surgery, September 1, 2007; 41(4): 277 - 293. [Abstract] [PDF]

				K. Bedard and K.-H. Krause The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology Physiol Rev, January 1, 2007; 87(1): 245 - 313. [Abstract] [Full Text] [PDF]

				M. C. Perianayagam, O. Liangos, A. Y. Kolyada, R. Wald, R. W. MacKinnon, L. Li, M. Rao, V. S. Balakrishnan, J. V. Bonventre, B. J. Pereira, et al. NADPH Oxidase p22phox and Catalase Gene Variants Are Associated with Biomarkers of Oxidative Stress and Adverse Outcomes in Acute Renal Failure J. Am. Soc. Nephrol., January 1, 2007; 18(1): 255 - 263. [Abstract] [Full Text] [PDF]

				R. M. Taylor, D. Baniulis, J. B. Burritt, J. M. Gripentrog, C. I. Lord, M. H. Riesselman, W. S. Maaty, B. P. Bothner, T. E. Angel, E. A. Dratz, et al. Analysis of Human Phagocyte Flavocytochrome b558 by Mass Spectrometry J. Biol. Chem., December 1, 2006; 281(48): 37045 - 37056. [Abstract] [Full Text] [PDF]

				K. Doi, E. Noiri, A. Nakao, T. Fujita, S. Kobayashi, and K. Tokunaga Functional Polymorphisms in the Vascular Endothelial Growth Factor Gene Are Associated with Development of End-Stage Renal Disease in Males J. Am. Soc. Nephrol., March 1, 2006; 17(3): 823 - 830. [Abstract] [Full Text] [PDF]

				L. Wojnowski, B. Kulle, M. Schirmer, G. Schluter, A. Schmidt, A. Rosenberger, S. Vonhof, H. Bickeboller, M. R. Toliat, E.-K. Suk, et al. NAD(P)H Oxidase and Multidrug Resistance Protein Genetic Polymorphisms Are Associated With Doxorubicin-Induced Cardiotoxicity Circulation, December 13, 2005; 112(24): 3754 - 3762. [Abstract] [Full Text] [PDF]

				F. R. Sheppard, M. R. Kelher, E. E. Moore, N. J. D. McLaughlin, A. Banerjee, and C. C. Silliman Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation J. Leukoc. Biol., November 1, 2005; 78(5): 1025 - 1042. [Abstract] [Full Text] [PDF]

				J. A. Leopold and J. Loscalzo Oxidative Enzymopathies and Vascular Disease Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1332 - 1340. [Abstract] [Full Text] [PDF]

				R. M. Touyz Reactive Oxygen Species, Vascular Oxidative Stress, and Redox Signaling in Hypertension: What Is the Clinical Significance? Hypertension, September 1, 2004; 44(3): 248 - 252. [Abstract] [Full Text] [PDF]