Objectives: The –765G>C variation (rs20417 SNP) in the promoter of cyclooxygenase-2 (COX-2) gene has been demonstrated to lower COX-2 enzyme activity in the vasculature, thus affecting atherosclerotic plaque growth and stability. Therefore, this genetic variant may be a candidate influencing the residual risk. Methods: In 285 coronary patients the incidence of major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular deaths, non-fatal myocardial infarction and stroke, unstable angina and revascularization procedures, was monitored for a median of 7.8 years. The genotypes were obtained in 231 patients (81%) by PCR amplification and FAU I digestion. Results: 89 MACEs (38.5%) were recorded during the follow-up in genotyped patients. Their incidence was not different in patients with GC or CC when compared with those with GG genotype (46.2 vs. 35.5% respectively; p = 0.14). Kaplan-Meyer analysis did not demonstrate any influence of COX-2 genotypes on the event-free survival time (log-rank p = 0.55). After controlling for confounders, the –765G>C carrier status was not associated with significant variation in the risk of MACE or its individual components. Conclusions: These results suggest that the functional G–765C variant in the COX-2 gene is not a significant predictor of the recurrence of ischemic events in coronary patients.

Cholesterol Treatment Trialists’ (CTT) Collaborators: Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366:1267–1278.
LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK, Treating to New Targets (TNT) Investigators: Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425–1435.
Arca M, Montali A, Valiante S, Campagna F, Pigna G, Paoletti V, Antonini R, Barillà F, Tanzilli G, Vestri A, Gaudio C: Usefulness of atherogenic dyslipidemia for predicting cardiovascular risk in patients with angiographically defined coronary artery disease. Am J Cardiol 2007;100:1511–1516.
Libby P, Ridker PM, Maseri A: Inflammation and atherosclerosis. Circulation 2002;105:1135–1143.
Belton O, Byrne D, Kearney D, Leahy A, Fitzgerald DJ: Cyclooxygenase-1 and -2-dependent prostacyclin formation in patients with atherosclerosis. Circulation 2000;102:840–845.
Gómez-Hernández A, Martín-Ventura JL, Sánchez-Galán E, Vidal C, Ortego M, Blanco-Colio LM, Ortega L, Tuñón J, Egido J: Overexpression of COX-2, prostaglandin E synthase-1 and prostaglandin E receptors in blood mononuclear cells and plaque of patients with carotid atherosclerosis: regulation by nuclear factor-ĸB. Atherosclerosis 2006;187:139–149.
Cipollone F, Fazia M, Iezzi A, Pini B, Cuccurullo C, Zucchelli M, de Cesare D, Ucchino S, Spigonardo F, De Luca M, Muraro R, Bei R, Bucci M, Cuccurullo F, Mezzetti A: Blockade of the angiotensin II type 1 receptor stabilizes atherosclerotic plaques in humans by inhibiting prostaglandin E2-dependent matrix metalloproteinase activity. Circulation 2004;109:1482–1488.
Cipollone F, Prontera C, Pini B, Marini M, Fazia M, De Cesare D, Iezzi A, Ucchino S, Boccoli G, Saba V, Chiarelli F, Cuccurullo F, Mezzetti A: Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E2-dependent plaque instability. Circulation 2001;104:921–927.
Cipollone F, Fazia ML: COX-2 and atherosclerosis. J Cardiovasc Pharmacol 2006;47(suppl 1):S26–S36.
Fritsche E, Baek SJ, King LM, Zeldin DC, Eling TE, Bell DA: Functional Characterization of cyclooxygenase-2 polymorphisms. J Pharmacol Exp Ther 2001;299:468–476.
Papafili A, Hill MR, Brull DJ, McAnulty RJ, Marshall RP, Humphries SE, Laurent GJ: Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response. Arterioscler Thromb Vasc Biol 2002;22:1631–1636.
Cipollone F, Patrono C: Cyclooxygenase-2 polymorphism. Putting a brake on the inflammatory response to vascular injury? Arterioscer Thromb Vasc Biol 2002;22:1516–1518.
Corella D, González JI, Bulló M, Carrasco P, Portolés O, Díez-Espino J, Covas MI, Ruíz-Gutierrez V, Gómez-Gracia E, Arós F, Fiol M, Herrera MC, Santos JM, Sáez G, Lamuela R, Lahoz C, Vinyoles E, Ros E, Estruch R: Polymorphisms cyclooxygenase-2 –765G>C and interleukin-6 –174G>C are associated with serum inflammation markers in a high cardiovascular risk population and do not modify the response to a Mediterranean diet supplemented with virgin olive oil or nuts. Nutr 2009;139:128–134.
Orbe J, Beloqui O, Rodriguez JA, Belzunce MS, Roncal C, Páramo JA: Protective effect of the G–765C COX-2 polymorphism on subclinical atherosclerosis and inflammatory markers in asymptomatic subjects with cardiovascular risk factors. Clin Chim Acta 2006;368:138–143.
Cipollone F, Toniato E, Martinetti S, Fazia M, Iezzi A, Cuccurullo C, Pini B, Ursi S, Vitullo S, Averna M, Arca M, Montali A, Campagna F, Ucchino S, Spigonardo F, Taddei S, Virdis A, Ciabattoni G, Notarbartolo A, Cuccurullo F, Mezzetti A: A polymorphism in the cycloxygenase-2 gene as an inherited protective factors against myocardial infarction and stroke. JAMA 2004;291:2221–2228.
Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology: Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J 2007;28:1598–1660.
Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O’Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A: Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997;350:757–764.
Hegener HH, Diehl KA, Kurth T, Gaziano JM, Ridker PM, Zee RY: Polymorphisms of prostaglandin-endoperoxide synthase-2 gene, and prostaglandin-E receptor 2 gene, C-reactive protein concentrations and risk of atherothrombosis: a nested case-control approach. J Thromb Haemost 2006;4:1718–1722.
Lee CR, North KE, Bray MS, Couper DJ, Heiss G, Zeldin DC: Cyclooxygenase polymorphisms and risk of cardiovascular events: the Atherosclerosis Risk in Communities (ARIC) study. Clin Pharmacol Ther 2008;83:52–60.
Kohsaka S, Volcik KA, Folsom AR, Wu KK, Ballantyne CM, Willerson JT, Boerwinkle E: Increased risk of incident stroke associated with the cyclooxygenase 2 G–765C polymorphism in African-Americans: the Atherosclerosis Risk in Communities Study. Atherosclerosis 2008;196:926–930.
Colaizzo D, Fofi L, Tiscia G, Guglielmi R, Cocomazzi N, Prencipe M, Margaglione M, Toni D: The COX-2 G/C –765 polymorphism may modulate the occurrence of cerebrovascular ischemia. Blood Coagul Fibrinolysis 2006;17:93–96.
Mosheimer BA, Kaneider NC, Feistritzer C, Djanani A, Sturn DH, Patsch JR, Wiedermann CJ: CD40-ligand-dependent induction of COX-2 gene expression in endothelial cells by activated platelets: inhibitory effects of atorvastatin. Blood Coagul Fibrinolysis 2005;16:105–110.
Huuskonen KH, Kunnas TA, Tanner MM, Mikkelsson J, Ilveskoski E, Karhunen PJ, Nikkari ST: COX-2 gene promoter polymorphism and coronary artery disease in middle-aged men: the Helsinki Sudden Death Study. Mediators Inflamm 2008;2008:289453.
Arca M, Conti B, Montali A, Pignatelli P, Campagna F, Verna R, Vestri A, Gaudio C, Violi F: C242T polymorphism of NADPH oxidase p22phox, markers of oxidative stress and recurrences of cardiovascular events in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2008;28:752–777.
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