Abstract
Coronary artery disease (CAD) is a multifactorial disease that results from the interaction between genetic and traditional risk factors. The endothelium dysfunction plays a key role in the progression of atherosclerotic lesions. E-selectin is a marker of endothelium dysfunction. The aim of the present study was to find a relationship between 561A > C and 98G > T polymorphisms of E-selectin gene and CAD as well as interactions between these polymorphic variants and traditional risk factors of the disease in determining the susceptibility to CAD. The study population included 191 patients with angiographically documented CAD and 203 blood donors. The analysis of genetic polymorphisms was performed using the polymerase chain reaction-restriction fragment length polymorphism method. We found that the frequencies of 561C and 98T alleles of E-selectin gene and carriers of C and T alleles were similar in the entire groups as well as in the age-and sex-matched subgroups. We observed a strong significant correlation between those two polymorphisms; almost all subjects possessing one “proatherosclerotic” allele of E-selectin gene also had the second allele (r = 0.963, P < 0.0001). There were also synergistic effects between both polymorphisms and hypercholesterolemia (but not with smoking or overweight) in determining the susceptibility to CAD. The present study points to synergistic interactions between 561A > C or 98G > T polymorphisms of E-selectin gene and hypercholesterolemia that cause a significant increase in the susceptibility to CAD.
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Gensini GF, Comeglio M, Colella A (1998) Classical risk factors and emerging elements in the risk profile for coronary artery disease. Eur Heart J 19Suppl A:A53–A61
Frenette PS, Wagner DD (1997) Insights into selectin function from knockout mice. Thromb Haemostasis 78:60–64
Bevilacqua MP, Nelson RM (1993) Selectins. J Clin Invest 91: 379–387
Tedder TF, Steeber DA, Chen A, Engel P (1995) The selectins: vascular adhesion molecules. FASEB J 9:866–873
Jung U, Norman KE, Scharffetter-Kochanek K, Beaudet AL, Ley K (1998) Transit time of leukocytes rolling through venules controls cytokine-induced inflammatory cell recruitment in vivo. J Clin Invest 102:1526–1533
Kunkel EJ, Ley K (1996) Distinct phenotype of E-selectindeficient mice. E-selectin is required for slow leukocyte rolling in vivo. Circ Res 79:1196–1204
Ley K, Allietta M, Bullard DC, Morgan S (1998) Importance of E-selectin for firm leukocyte adhesion in vivo. Circ Res 83: 287–294
Zak I, Lewandowska E, Gnyp W (2000) Selectin glycoprotein ligands. Acta Biochim Pol 47:393–412
Wenzel K, Hanke R, Speer A (1994) Polymorphism in the human E-selectin gene detected by PCR-SSCP. Hum Genet 94:452–453
Wenzel K, Felix S, Kleber FX, Brachold R, Menke T, Schattke S, Schulte KL, Gläser C, Rohde K, Baumann G, Speer A (1994) Eselectin polymorphism and atherosclerosis: an association study. Hum Mol Genet 3:1935–1937
Zheng F, Chevalier JA, Zhang LQ, Virgil D, Ye SQ, Kwiterovich PO (2001) An HphI polymorphism in the E-selectin gene is associated with premature coronary artery disease. Clin Genet 59: 58–64
Alpert JS, Thygesen K (2000) Myocardial infarction redefined — a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 21:1502–1513
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma without the use of preparative centrifuge. Clin Chem 18:499–502
Ye SQ, Usher D, Virgil D, Zhang LQ, Yochim SE, Gupta R (1999) A PstI polymorphism detects the mutation of serine 128 to arginine in CD 62E gene — a risk factor for coronary artery disease. J Biomed Sci 6:18–21
Khoury MJ, Flanders WD (1996) Nontraditional epidemiologic approaches in the analysis of gene-environment interaction: case-control studies with no controls! Am J Epidemiol 144:207–213
Tangurek B, Ozer N, Sayar N, Terzi S, Yilmaz H, Dayi SU, Ciloglu F, Aksu H, Asilturk R, Cagil A (2006) The relationship between endothelial nitric oxide synthase gene polymorphism (T-786 C) and coronary artery disease in the Turkish population. Heart Vessels 21:285–290
Zak I, Balcerzyk A, Sarecka B, Niemiec P, Ciemniewski Z, Dylag S (2005) Contemporaneous carrier-state of two or three “proatherosclerotic” variants of APOE, ICAM1, PPARA and PAI-1 genes differentiate CAD patients from healthy individuals. Clin Chim Acta 362:110–118
Kansas GS (1996) Selectins and their ligands: current concepts and controversies. Blood 88:3259–3287
Cominacini L, Fratta Pasini A, Garbin U, Campagnola M, Davoli A, Rigoni A, Zenti MG, Pastorino AM, Lo Cascio V (1997) E-selectin plasma concentration is influenced by glycaemic control in NIDDM patients: possible role of oxidative stress. Diabetologia 40:584–589
Takahashi Y, Mai M, Watanabe M, Tokiwa M, Nishioka K (1998) Relationship between serum ELAM-1 and metastasis among patients with colon cancer. Dis Colon Rectum 41:770–774
Rauchhaus M, Gross M, Schulz S, Francis DP, Greiser P, Norwig A, Weidhase L, Coats AJ, Dietz R, Anker SD, Gläser C (2002) The E-selectin SER128ARG gene polymorphism and restenosis after successful coronary angioplasty. Int J Cardiol 83:249–257
Bannan S, Mansfield MW, Grant PJ (1998) Soluble vascular cell adhesion molecule-1 and E-selectin levels in relation to vascular risk factors and to E-selectin genotype in the first degree relatives of NIDDM patients and in NIDDM patients. Diabetologia 41: 460–466
Mlekusch W, Exner M, Schillinger M, Sabeti S, Mannhalter C, Minar E, Wagner O (2004) E-Selectin and restenosis after femoropopliteal angioplasty: prognostic impact of the Ser128Arg genotype and plasma levels. Thromb Haemost 91:171–179
Thorand B, Baumert J, Döring A, Schneider A, Chambless L, Löwel H, Kolb H, Koenig W (2006) Association of cardiovascular risk factors with markers of endothelial dysfunction in middle-aged men and women. Results from the MONICA/KORA Augsburg Study. Thromb Haemost 95:134–141
Demerath E, Towne B, Blangero J, Siervogel RM (2001) The relationship of soluble ICAM-1, VCAM-1, P-selectin and E-selectin to cardiovascular disease risk factors in healthy men and women. Ann Hum Biol 28:664–678
Mizia-Stec K, Zahorska-Markiewicz B, Gasior Z (2004) Cigarette smoking and inflammatory indices in coronary artery disease. Int J Cardiol 93:169–174
Wenzel K, Ernst M, Rohde K, Baumann G, Speer A (1996) DNA polymorphisms in adhesion molecule genes — a new risk factor for early atherosclerosis. Hum Genet 97:15–20
Glowinska B, Urban M, Peczynska J, Florys B (2005) Soluble adhesion molecules (sICAM-1, sVCAM-1) and selectins (sE selectin, sP selectin, sL selectin) levels in children and adolescents with obesity, hypertension, and diabetes. Metabolism 54:1020–1026
Kvasnicka T, Kvasnicka J, Ceska R, Grauova B, Vrablik M (2001) Increasing plasma levels of soluble cell adhesion molecules (sESelectin, sP-Selectin and sICAM-1) in overweight adults with combined hyperlipidemia. Sb Lek 102:473–477
Niemiec P, Zak I, Wita K (2007) The 242T variant of the CYBA gene polymorphism increases the risk of coronary artery disease associated with cigarette smoking and hypercholesterolemia. Coron Artery Dis 18:339–346
Balcerzyk A, Zak I, Krauze J (2007) Synergistic effects between Q192R polymorphism of paraoxonase 1 gene and some conventional risk factors in premature coronary artery disease. Arch Med Res 38:545–550
Tartan Z, Orhan G, Kasikçioglu H, Uyarel H, Unal S, Ozer N, Ozay B, Ciloglu F, Cam N (2007) The role of paraoxonase (PON) enzyme in the extent and severity of the coronary artery disease in type-2 diabetic patients. Heart Vessels 22:158–164
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Zak, I., Sarecka, B. & Krauze, J. Synergistic effects between 561A > C and 98G > T polymorphisms of E-selectin gene and hypercholesterolemia in determining the susceptibility to coronary artery disease. Heart Vessels 23, 257–263 (2008). https://doi.org/10.1007/s00380-008-1040-2
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DOI: https://doi.org/10.1007/s00380-008-1040-2