Association of factor II G20210A, factor V G1691A and methylenetetrahydrofolate reductase C677T gene polymorphism with different forms of myocardial infarction: ST segment elevation and non-ST segment elevation

Milica Ćućuz JokIć; Vesna Ilić; Bojana Cikota-Aleksić; Slobodan Obradović; Zvonko Magić

doi:10.2298/VSP180621170C

Milica Ćućuz JokIć Military Medical Academy, Institut of Medical Research, Belgrade, Serbia
Vesna Ilić Military Medical Academy, Institut of Medical Research, Belgrade, Serbia
Bojana Cikota-Aleksić Military Medical Academy, Institut of Medical Research, Belgrade, Serbia
Slobodan Obradović University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
Zvonko Magić Military Medical Academy, Institut of Medical Research, Belgrade, Serbia

DOI: https://doi.org/10.2298/VSP180621170C

Keywords: genes, factor v, prothrombin, st elevation myocardial infarction, non-st elevated myocardial infarction, polymorphism, genetic, risk factor

Abstract

Background/Aim. Coagulation Factor II G20210A and Factor V G1691A variants are moderately associated with coronary artery disease. Polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene C677T is associated with myocardial infarction (MI) in some ethnical groups. At the present time there are rare studies which try to differentiate two forms of MI, ST-elevation MI (STEMI) and non ST-elevation MI (NSTEMI) according to the genetic background. The aim of the study was investigate the association of polymorphisms of Factor II G20210A, Factor V G1691A and MTHFR C677T with different forms of MI: STEMI and NSTEMI. Methods. The study included 82 patients, divided into two cohorts: patients with STEMI (49 patients) and NSTEMI (33 patients). Genetic factors that would be different in those two entities, included in response to plaque rupture and occlusion of coronary artery, were examined. The peripheral blood lymphocytes were used as DNA source. Genotypes were determined on the polymerase chain reaction (PCR) based methodology. Results. The frequency of MTHFR C677T CT genotype was higher in the patients with NSTEMI in comparison with the patients with STEMI [odds ratio (OR) 3.33; 95% confidence interval (CI) 1.22–9.15; p = 0.02]. Logistic regression analysis shows MTHFR CT genotype as an independent prognostic factor for development of NSTEMI (OR 3.15; 95% CI 1.20–8.29; p = 0.02). There were no differences between two patients groups in frequency of Factor II G20210A and Factor V G1691A gene polymorphism. Conclusion. MTHFR C677T CT genotype was significantly associated with the NSTEMI development examined patients.

References

Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859): 2095–128.

Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial in-farction. Eur Heart J 2012; 33(20): 2551–67.

Lee CW, Hwang I, Park CS, Lee H, Park DW, Kang SJ, et al. Comparison of intravascular ultrasound and histological find-ings in culprit coronary plaques between ST-segment elevation and non-ST-segment elevation myocardial infarction. Am J Cardiol 2013; 112(1): 68–72.

Dong L, Mintz GS, Witzenbichler B, Metzger DC, Rinaldi MJ, Duffy PL, et al. Comparison of plaque characteristics in nar-rowings with ST-elevation myocardial infarction (STEMI), non-STEMI/unstable angina pectoris and stable coronary ar-tery disease (from the ADAPT-DES IVUS Substudy). Am J Cardiol 2015; 115(7): 860–6.

Rott D, Weiss AT, Chajek-Shaul T, Leibowitz D. ST-Deviation Patterns in Recurrent Myocardial Infarctions. Am J Cardiol 2006; 98(1): 10–3.

Dai X, Wiernek S, Evans JP, Runge MS. Genetics of coronary artery disease and myocardial infarction. World J Cardiol 2016; 8(1): 1–23.

Roberts R. Genetics of coronary artery disease. Circ Res 2014; 114(12): 1890–903.

Klerk M, Verhoef P. Methylenetetrahydrofolate Reductase 677C→T Polymorphism and Risk of Arterial Occlusive Dis-ease. In: Ueland PM, Rozen R, editors. MTHFR Polymor-phisms and Disease. Georgetown, Texas, USA: Eure-kah.com/Landes Bioscience; 2005. p. 100‒12.

Keijzer M, den Heijer M. Methylenetetrahydrofolate Reductase and Venous Thrombosis. In: Ueland PM, Rozen R, editors. MTHFR Polymorphisms and Disease. Georgetown, Texas, USA: Eurekah.com/Landes Bioscience; 2005. p. 113‒24.

Sode BF, Allin KH, Dahl M, Gyntelberg F, Nordestgaard BG. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type. CMAJ 2013; 185(5): E229‒37.

Ye Z, Liu EH, Higgins JP, Keavney BD, Lowe GD, Collins R, et al. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 2006; 367(9511): 651‒8.

Payne DA, Chamoun AJ, Seifert SL, Stouffer GA. MTHFR 677 C-->T mutation: a predictor of early-onset coronary artery disease risk. Thromb Res 2001; 103(4): 275‒9.

Isordia-Salas I, Trejo-Aguilar A, Valadés-Mejía MG, Santiago-Germán D, Leaños-Miranda A, Mendoza-Valdéz L, et al. C677T polymorphism of the 5,10 MTHFR gene in young Mexican subjects with ST-elevation myocardial infarction. Arch Med Res 2010; 41(4): 246‒50.

Rogers EJ, Chen S, Chan A. Folate deficiency and plasma ho-mocysteine during increased oxidative stress. N Engl J Med 2007; 357(4): 421‒2.

Tsuda K, Nishio I. Serum homocysteine and endothelial dys-function in circulatory disorders in women. Circulation 2004; 110(4): e37.

Harmon DL, Woodside JV, Yarnell JW, McMaster D, Young IS, McCrum EE, et al. The common 'thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia. QJM 1996; 89(8): 571‒7.

Kluijtmans LA, Kastelein JJ, Lindemans J, Boers GH, Heil SG, Bruschke AV, et al. Thermolabile methylenetetrahydrofolate reductase in coronary artery disease. Circulation 1997; 96(8): 2573‒7.

O'Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the man-agement of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61(4): e78‒e140.

Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coro-nary Syndromes: a report of the American College of Cardiol-ogy/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 64(24): e139‒e228.

Miller SA, Dykes DD, Polesky HF. A simple salting out proce-dure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16(3): 1215.

Žaliaduonytė-Pekšienė D, Lesauskaitė V, Liutkevičienė R, Tamakauskas V, Kviesulaitis V, Šinkūnaitė-Maršalkienė G, et al. Association of the genetic and traditional risk factors of is-chemic heart disease with STEMI and NSTEMI development. J Renin Angiotensin Aldosterone Syst 2017; 18(4): 1470320317739987.

Miyachi H, Takagi A, Miyauchi K, Yamasaki M, Tanaka H, Yo-shikawa M, et al. Current characteristics and management of ST elevation and non-ST elevation myocardial infarction in the Tokyo metropolitan area: from the Tokyo CCU network registered cohort. Heart Vessels 2016; 31(11): 1740‒51.

Belle L, Cayla G, Cottin Y, Coste P, Khalife K, Labèque JN, et al. French Registry on Acute ST-elevation and non-ST-elevation Myocardial Infarction 2015 (FAST-MI 2015). Design and baseline data. Arch Cardiovasc Dis 2017; 110(6‒7): 366‒78.

Di Stefano R, Di Bello V, Barsotti MC, Grigoratos C, Armani C, Dell'Omodarme M, et al. Inflammatory markers and cardiac function in acute coronary syndrome: difference in ST-segment elevation myocardial infarction (STEMI) and in non-STEMI models. Biomed Pharmacother 2009; 63(10): 773‒80.

Habib SS, Kurdi MI, Al Aseri Z, Suriya MO. CRP levels are higher in patients with ST elevation than non-ST elevation acute coronary syndrome. Arq Bras Cardiol 2011; 96(1): 13‒7. (English, Portuguese, Spanish)

Ezzat H, Attia FA, Mokhar A, El-Tokhy HM, Alalfy NM, Elk-houly NY. Prevalence of trombophilic gene polymorphisms (FVL G1691A and MTHFR C677T) in patients with myocar-dial infarction. Egypt J Med Hum Gen. 2014; 15(2): 113‒23.

Dai X, Wiernek S, Evans JP, Runge MS. Genetics of coronary artery disease and myocardial infarction. World J Cardiol 2016; 8(1): 1‒23.

Xuan C, Bai XY, Gao G, Yang Q, He GW. Association be-tween polymorphism of methylenetetrahydrofolate reductase (MTHFR) C677T and risk of myocardial infarction: a meta-analysis for 8,140 cases and 10,522 controls. Arch Med Res 2011; 42(8): 677‒85.

Wilcken B, Bamforth F, Li Z, Zhu H, Ritvanen A, Renlund M, et al. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet 2003; 40(8): 619‒25.

Alizadeh S, Djafarian K, Moradi S, Shab-Bidar S. C667T and A1298C polymorphisms of methylenetetrahydrofolate reduc-tase gene and susceptibility to myocardial infarction: A sys-tematic review and meta-analysis. Int J Cardiol 2016; 217: 99‒108.

Ho CH, Kuo BI, Kong CW, Chau WK, Hsu HC, Gau JP, et al. Influence of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, B vitamins and other factors on plasma homocysteine and risk of thromboembolic disease in Chinese. J Chin Med Assoc 2005; 68(12): 560‒5.

Kluijtmans LA, Whitehead AS. Methylenetetrahydrofolate re-ductase genotypes and predisposition to atherothrombotic dis-ease; evidence that all three MTHFR C677T genotypes confer different levels of risk. Eur Heart J 2001; 22(4): 294‒9.