Abstract
The p22phox protein subunit is essential for NADPH oxidase activity. The prevalence of C242T variants of p22phox gene was studied in 101 healthy Egyptian controls and 104 acute myocardial infarction (AMI) Egyptian patients. Contribution of oxidative stress, represented by serum oxidized-LDL (ox-LDL), in development of AMI was also examined and correlated with C242T gene variants. Genotyping and ox-LDL were assessed by PCR–RFLP and ELISA. Results showed that wild type CC genotype is prevalent in 27 % of controls; CT and TT are in 72 and 1 %. In patients, the distribution was 40.2, 59.8 and 0 % for CC, CT and TT; respectively, showing a significant difference (p = 0.0259). Serum ox-LDL levels were higher in patients than controls (p ≤ 0.0001). Subjects having CT genotype had lower levels of ox-LDL than CC genotype (p ≤ 0.005). C242T polymorphism of p22phox gene of NADPH oxidase is a novel genetic marker associated with reduced susceptibility to AMI.
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Tobin MD, Braund PS, Burton PR, Thompson JR, Steeds R, Channer K, Cheng S, Lindpaintner K, Samani NJ (2004) Genotypes and haplotypes predisposing to myocardial infarction: a multilocus case-control study. Eur Heart J 25:459–467
Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H, Sone T, Tanaka M, Yokota M (2002) Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med 347:1916–1923
Guzik TJ, Sadowski J, Guzik B, Jopek A, Kapelak B, Przybyowski P, Wierzbicki K, Korbut R, Harrison DG, Channon KM (2006) Coronary artery superoxide production and nox isoform expression in human coronary artery disease. Arterioscler Thromb Vasc Biol 26:333–339
Inoue N, Kawashima S, Kanazawa K, Yamada S, Akita H, Yokoyama M (1998) Polymorphism of the NADH/NADPH oxidase p22 phox gene in patients with coronary artery disease. Circulation 97:135–137
Guzik TJ, West NE, Black E, McDonald D, Ratnatunga C, Pillai R, Channon KM (2000) Functional effect of the C242T polymorphism in the NAD(P)H oxidase p22phox gene on vascular superoxide production in atherosclerosis. Circulation 102:1744–1747
Wyche KE, Wang SS, Griendling KK, Dikalov SI, Austin H, Rao S, Fink B, Harrison DG, Zafari AM (2004) C242T CYBA polymorphism of the NADPH oxidase is associated with reduced respiratory burst in human neutrophils. Hypertension 43:1246–1251
Sorescu D, Weiss D, Lassegue B, Clempus RE, Szocs K, Sorescu GP, Valppu L, Quinn MT, Lambeth JD, Vega JD, Taylor WR, Griendling KK (2002) Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation 105:1429–1435
Ridker P, Libby P (1998) Nontraditional coronary risk factors and vascular biology: the frontiers of preventive cardiology. J Invest Med 46:338–350
Ridker P, Cushman M, Stampfer M, Tracy RP, Hennekens CH (1997) Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 336:973–979
Fredrikson GN, Hedblad B, Berglund G, Nilsson J (2003) Plasma oxidized LDL: a predictor for acute myocardial infarction? J Intern Med 253:425–429
Glass CK, Witztum JL (2001) Atherosclerosis: the road ahead. Cell 104:503–516
Ehara S, Ueda M, Naruko T, Haze K, Itoh A, Otsuka M, Komatsu R, Matsuo T, Itabe H, Takano T, Tsukamoto Y, Yoshiyama M, Takeuchi K, Yoshikawa J, Becker AE (2001) Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 103:1955–1960
Greenspoon SA, Scarpetta MA, Drayton ML (1998) QIAamp spin columns as a method of DNA isolation for forensic casework. J Forensic Sci 43:1024–1030
Fahle GA, Fischer SH (2000) Comparison of six commercial DNA extraction kits for recovery of cytomegalovirus DNA from spiked human specimens. J Clin Microbiol 38:3860–3863
Craig WY (1995) Auto antibodies against oxidized low density lipoprotein: a review of clinical findings and assay methodology. J Clin Lab Anal 9:70–74
Lambeth JD (2004) NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4:181–189
Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313
Cave AC, Brewer AC, Narayanapanicker A, Ray R, Grieve DJ, Walker S, Shah AM (2006) NADPH oxidases in cardiovascular heth and disease. Antioxid Redox Signal 8:691–728
Lassegue B, Clempus RE (2003) Vascular NAD(P)H oxidases: specific features, expression, and regulation. Am J Physiol Regul Integr Comp Physiol Rev 285:R277–R297
Parkos CA, Dinauer MC, Walker LE, Allen RA, Jesaitis AJ, Orkin SH (1988) Primary structure and unique expression of the 22-kilodalton light chain of human neutrophil cytochrome b. Proc Natl Acad Sci USA 85:3319–3323
Fang S, Wang L, Jia C (2010) Association of p22phox gene C242T polymorphism with coronary artery disease: a meta-analysis. Thromb Res 125:e197–e201
Lee WH, Hwang TH, Oh GT, Kwon SU, Choi YH, Park JE (2001) Genetic factors associated with endothelial dysfunction affect the early onset of coronary artery disease in Korean males. Vasc Med 6:103–108
He MA, Cheng LX, Jiang CZ, Zeng HS, Wang J, Wang F, Chen Y, Yang M, Tan H, Zheng HY, Hu FB, Wu TC (2007) Associations of polymorphism of P22(phox) C242T, plasma levels of vitamin E, and smoking with coronary heart disease in China. Am Heart J 153:e1–e6
Fan M, Kahonen M, Rontu R, Lehtinen R, Viik J, Niemi M, Nieminen T, Niemela K, Porsti I, Koobi T, Turjanmaa V (2006) The p22phox C242T gene polymorphism is associated with a reduced risk of angiographically verified coronary artery disease in a high-risk Finnish Caucasian population. The Finnish Cardiovascular Study. Am Heart J 152:538–542
Schachinger V, Britten MB, Dimmeler S, Zeiher AM (2001) NADH/NADPH oxidase p22 phox gene polymorphism is associated with improved coronary endothelial vasodilator function. Eur Heart J 22:96–101
Ito D, Murata M, Watanabe K, Yoshida T, Saito I, Tanahashi N, Fukuuchi Y (2000) C242T polymorphism of NADPH oxidase p22 PHOX gene and ischemic cerebrovascular disease in the Japanese population. Stroke 31:936–939
Nasti S, Spallarossa P, Altieri P, Garibaldi S, Fabbi P, Polito L, Bacino L, Brunelli M, Brunelli C, Barsotti A, Ghigliotti G (2006) C242T polymorphism in CYBA gene (p22phox) and risk of coronary artery disease in a population of Caucasian Italians. Dis Markers 22:167–173
Saha N, Sanghera DK, Kamboh MI (1999) The p22 phox polymorphism C242T is not associated with CHD risk in Asian Indians and Chinese. Eur J Clin Invest 29:999–1002
Mata-Balaguer T, de la Herran R, Ruiz-Rejon C, Ruiz-Rejon M, Garrido-Ramos MA, Ruiz-Rejon F (2004) Angiotensin-converting enzyme and p22(phox) polymorphisms and the risk of coronary heart disease in a low-risk Spanish population. Int J Cardiol 95:145–151
van der Wal AC, Becker AE, van der Loos CM, Das PK (1994) Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 89:36–44
Katsura M, Forster LA, Ferns GAA, Anggarda EE (1994) Oxidative modification of low density lipoprotein by human polymorphonuclear leukocytes to a form recognized by the lipoprotein scavenger pathway. Biochim Biophys Acta 1213:231–237
Chen CH, Nguyen HH, Weilbaecher D, Luo S, Gotto AM, Henry PD (1995) Basic growth factor reverses atherosclerotic impairment of human coronary angiogenesis-like responses in vitro. Atherosclerosis 116:261–268
Holvoet P, Collen D (1997) Thrombosis and atherosclerosis. Curr Opin Lipidol 8:320–328
Holvoet P, Perez G, Zhao Z, Brouwers E, Bernar H, Collen D (1995) Malondialdehyde-modified low density lipoproteins in patients with atherosclerotic disease. J Clin Invest 95:2611–2619
Holvoet P, Vanhaecke J, Janssens S, Van de Werf F, Collen D (1998) Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease. Circulation 98:1487–1494
Vasankari T, Ahotupa M, Toikka J, Mikkola J, Irjala K, Pasanen P, Neuvonen K, Raitakari O, Viikari J (2001) Oxidized LDL and thickness of carotid intima-media are associated with coronary atherosclerosis in middle-aged men: lower levels of oxidized LDL with statin therapy. Atherosclerosis 155:403–415
Tsimikas S, Brilakis ES, Miller ER, McConnell JP, Lennon RJ, Kornman KS, Witztum JL, Berger PB (2005) Oxidized phospholipids, Lp(a) lipoproteins, and coronary artery disease. N Engl J Med 353:46–57
Okana RH, Yamasaki Y, Ohtoshi K, Yasuda T, Katakami N, Hirano T, Yoshino G, Kajimoto Y (2002) NAD(P)H oxidase p22 Phox C242T polymorphism affects LDL particle size and insulin resistance in Japanese subjects. J Atheroscler Thromb 9:200–205
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This study was supported by the Science and Technology Development Fund (STDF) Grant No. 2951.
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Hashad, I.M., Abdel Rahman, M.F., Abdel-Maksoud, S.M. et al. C242T polymorphism of NADPH oxidase p22phox gene reduces the risk of coronary artery disease in a random sample of Egyptian population. Mol Biol Rep 41, 2281–2286 (2014). https://doi.org/10.1007/s11033-014-3081-1
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DOI: https://doi.org/10.1007/s11033-014-3081-1