Integrin Beta-3 Gene Polymorphism and Risk for Myocardial Infarction in Premature Coronary Disease

Document Type : Research Paper


1 Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

2 Tarbiat Modarres University, Tehran, Iran


Background: Contradictory results have been obtained regarding the role of integrin, beta 3 (ITGB3) gene polymorphisms in occurrence of myocardial infarction (MI).
Objectives: We aimed to assess the association between 1565C/T polymorphism of ITGB3 gene and increased risk for acute MI in patients with premature coronary artery disease (CAD).
Material and Methods: Our study included 1000 premature CAD patients that classified into two groups with history of MI (n = 461) and without of MI (n = 539). The polymorphism variants in 10% of samples were determined by PCR-RFLP technique and genotyping of the polymorphism in all subjects was conducted by High Resolution Melting method. Given the two conditions of patients residing in Tehran and also faced with their first episode of MI, 640 out of 1000 study samples that had been previously followed-up were assessed in a retrospective cohort phase regarding long-term major adverse cardiac events (MACE).
Results: There was no significant difference in the frequency of 1565C/T polymorphism between the MI and non-MI groups. The frequency of wild genotype was 69.2% and 72.2%, the frequency of homozygous genotype was 21.3% and 18.4%, and the frequency of mutant genotype was 9.5% and 9.5%, respectively (P = 0.505). No significant difference was also found in total-MACE free survival rate between the patients with different genotypes of 1565C/T polymorphism in both MI and non-MI group.
Conclusions: The carriage of the 1565C/T polymorphism of ITGB3 gene seems unlikely to be a significant risk factor for the development of MI in Iranian patients with premature CAD.


Main Subjects

1.           Banerjee A. A review of family history of cardiovascular disease: risk factor and research tool. Int J Clin Pract. 2012;66(6):536-543. doi: 10.1111/j.1742-1241.2012.02908.x pmid: 22607505
2.           McGillicuddy FC, Roche HM. Nutritional status, genetic susceptibility, and insulin resistance--important precedents to atherosclerosis. Mol Nutr Food Res. 2012;56(7):1173-1184. doi: 10.1002/mnfr.201100785 pmid: 22760984
3.           Roberts R, Stewart AF. The genetics of coronary artery disease. Curr Opin Cardiol. 2012;27(3):221-227. doi: 10.1097/HCO.0b013e3283515b4b pmid: 22382499
4.           Scheuner MT. Clinical application of genetic risk assessment strategies for coronary artery disease: genotypes, phenotypes, and family history. Prim Care. 2004;31(3):711-737, xi-xii. doi: 10.1016/j.pop.2004.04.001 pmid: 15331255
5.           Roberts R, Stewart AF. 9p21 and the genetic revolution for coronary artery disease. Clin Chem. 2012;58(1):104-112. doi: 10.1373/clinchem.2011.172759 pmid: 22015375
6.           Sharma RK, Voelker DJ, Sharma R, Reddy HK, Dod H, Marsh JD. Evolving role of platelet function testing in coronary artery interventions. Vasc Health Risk Manag. 2012;8:65-75. doi: 10.2147/VHRM.S28090 pmid: 22371653
7.           Lordkipanidze M. Platelet turnover in atherothrombotic disease. Curr Pharm Des. 2012;18(33):5328-5343. pmid: 22724418
8.           Freynhofer MK, Bruno V, Wojta J, Huber K. The role of platelets in athero-thrombotic events. Curr Pharm Des. 2012;18(33):5197-5214. pmid: 22724408
9.           Fintel DJ. Oral antiplatelet therapy for atherothrombotic disease: overview of current and emerging treatment options. Vasc Health Risk Manag. 2012;8:77-89. doi: 10.2147/VHRM.S26030 pmid: 22393298
10.        Reddy K, Khaliq A, Henning RJ. Recent advances in the diagnosis and treatment of acute myocardial infarction. World J Cardiol. 2015;7(5):243-276. doi: 10.4330/wjc.v7.i5.243 pmid: 26015857
11.        Barrett-Connor E, Giardina EG, Gitt AK, Gudat U, Steinberg HO, Tschoepe D. Women and heart disease: the role of diabetes and hyperglycemia. Arch Intern Med. 2004;164(9):934-942. doi: 10.1001/archinte.164.9.934 pmid: 15136300
12.        Wood D, De Backer G, Faergeman O, Graham I, Mancia G, Pyorala K. Prevention of coronary heart disease in clinical practice. Summary of recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. J Hypertens. 1998;16(10):1407-1414. pmid: 9814610
13.        Jomini V, Oppliger-Pasquali S, Wietlisbach V, Rodondi N, Jotterand V, Paccaud F, et al. Contribution of major cardiovascular risk factors to familial premature coronary artery disease: the GENECARD project. J Am Coll Cardiol. 2002;40(4):676-684. pmid: 12204497
14.        James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520. doi: 10.1001/jama.2013.284427 pmid: 24352797
15.        American Diabetes A. Standards of medical care in diabetes--2013. Diabetes Care. 2013;36 Suppl 1:S11-66. doi: 10.2337/dc13-S011 pmid: 23264422
16.        Haberbosch W, Rau M, Hehrlein FW, Tillmanns H, Philipp M, Katz N, et al. Association of the Platelet Glycoprotein IIIa PIA1/A2 Gene Polymorphism to Coronary Artery Disease but not to Nonfatal Myocardial Infarction in Low Risk Patients. Thrombosis Haemostasis. 2017;80(08):214-217. doi: 10.1055/s-0037-1615174
17.        Pastinen T, Perola M, Niini P, Terwilliger J, Salomaa V, Vartiainen E, et al. Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population. Hum Mol Genet. 1998;7(9):1453-1462. pmid: 9700201
18.        Tchoudakova DA, Minushkina LO, Zateyshchikov DA, Nosikov VV. Association of Polymorphic Marker A1/A2 of Gene ITGB3 with Coronary Artery Disease and Myocardial Infarction. Rus J Genet. 2004;40(10):1156-1158. doi: 10.1023/B:RUGE.0000044760.05694.d2
19.        Knowles JW, Wang H, Itakura H, Southwick A, Myers RM, Iribarren C, et al. Association of polymorphisms in platelet and hemostasis system genes with acute myocardial infarction. Am Heart J. 2007;154(6):1052-1058. doi: 10.1016/j.ahj.2007.05.021 pmid: 18035074
20.        Addad F, Elalamy I, Chakroun T, Abderrazek F, Dridi Z, Hamdi S, et al. Platelet glycoprotein IIIa (platelet antigen 1/platelet antigen 2) polymorphism and 1-year outcome in patients with stable coronary artery disease. Blood Coagul Fibrinolysis. 2010;21(7):674-678. doi: 10.1097/MBC.0b013e32833e47c1 pmid: 20739877
21.        Makeeva OA, Zykov MV, Golubenko MV, Kashtalap VV, Kuslish EV, Goncharova IA, et al. [The role of genetic factors in the prediction of myocardial infarction complications within one year follow up]. Kardiologiia. 2013;53(10):16-23. pmid: 24645551
22.        Verdoia M, Secco GG, Cassetti E, Schaffer A, Barbieri L, Perrone-Filardi P, et al. Platelet PIA1/PIA2 polymorphism and the risk of periprocedural myocardial infarction in patients with acute coronary syndromes undergoing coronary angioplasty. Blood Coagul Fibrinolysis. 2014;25(2):107-113. doi: 10.1097/MBC.0b013e3283650717 pmid: 24480844
23.        Marenberg ME, Risch N, Berkman LF, Floderus B, de Faire U. Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med. 1994;330(15):1041-1046. doi: 10.1056/NEJM199404143301503 pmid: 8127331
24.        Nora JJ, Lortscher RH, Spangler RD, Nora AH, Kimberling WJ. Genetic--epidemiologic study of early-onset ischemic heart disease. Circulation. 1980;61(3):503-508. pmid: 7353240
25.        Ardissino D, Mannucci PM, Merlini PA, Duca F, Fetiveau R, Tagliabue L, et al. Prothrombotic genetic risk factors in young survivors of myocardial infarction. Blood. 1999;94(1):46-51. pmid: 10381497
26.        Grove EL, Orntoft TF, Lassen JF, Jensen HK, Kristensen SD. The platelet polymorphism PlA2 is a genetic risk factor for myocardial infarction. J Intern Med. 2004;255(6):637-644. doi: 10.1111/j.1365-2796.2004.01327.x pmid: 15147527
27.        Lopes NH, Pereira AC, Hueb W, Soares PR, Lanz JR, Gersh BJ, et al. Effect of glycoprotein IIIa PlA2 polymorphism on outcome of patients with stable coronary artery disease and effect of smoking. Am J Cardiol. 2004;93(12):1469-1472. doi: 10.1016/j.amjcard.2004.03.005 pmid: 15194015
28.        Schwartz E, Demidova D, Sirotkina O, Kudinov S. The combination of glycoprotein IIIa PlA polymorphism with polymorphism of serotonin transporter as an independent strong risk factor for the occurrence of coronary thrombosis. Mol Genet Metab. 2003;79(3):229-230. pmid: 12855229
29.        Sentí M, Aubó C, Bosch M. The relationship betwen smoking and triglyceride-rich lipoproteins is modulated by genetic variation in the glycoprotein IIIa gene. Metabolism. 1998;47(9):1040-1041. doi: 10.1016/s0026-0495(98)90274-8