International Cardiovascular Research Journal

Published by: Kowsar

The Severity of Coronary Artery Disease and Methylenetetrahydrofolate Reductase (MTHFR) Enzyme Gene Polymorphism

Fatma Demet Ince 1 , * , Aysenur Atay 2 , Mehmet Hicri Koseoglu 2 , Hamit Yasar Ellidag 3 , Murat Yesil 4 and Erdal Deveci 4
Authors Information
1 Department of Clinical Biochemistry, Tepecik Training and Research Hospital, Izmir, Turkey
2 Department of Clinical Biochemistry, Ataturk Training and Research Hospital, Izmir, Turkey
3 Department of Clinical Biochemistry, Antalya Training and Research Hospital, Antalya, Turkey
4 Department of Cardiology, Ataturk Training and Research Hospital, Izmir, Turkey
Article information
  • International Cardiovascular Research Journal: 10 (4); e9805
  • Published Online: October 1, 2016
  • Article Type: Research Article
  • Received: December 2, 2015
  • Revised: February 26, 2016
  • Accepted: April 26, 2016

To Cite: Ince F D, Atay A, Koseoglu M H, Ellidag H Y, Yesil M, et al. The Severity of Coronary Artery Disease and Methylenetetrahydrofolate Reductase (MTHFR) Enzyme Gene Polymorphism, Int Cardio Res J. Online ahead of Print ; 10(4):e9805.

Copyright © 2016, Shiraz University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Objectives
3. Methods
4. Results
5. Discussion
  • 1. Montalescot G. Homocysteine: the new player in the field of coronary risk. Heart. 1996; 76(2): 101-2[PubMed]
  • 2. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA. 1995; 274(13): 1049-57[PubMed]
  • 3. Homberger A, Linnebank M, Winter C, Willenbring H, Marquardt T, Harms E, et al. Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene. Eur J Hum Genet. 2000; 8(9): 725-9[DOI][PubMed]
  • 4. Peng F, Labelle LA, Rainey BJ, Tsongalis GJ. Single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene are common in US Caucasian and Hispanic American populations. Int J Mol Med. 2001; 8(5): 509-11[PubMed]
  • 5. Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, et al. Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation. 1997; 95(8): 2032-6[PubMed]
  • 6. Shpichinetsky V, Raz I, Friedlander Y, Goldschmidt N, Wexler ID, Ben-Yehuda A, et al. The association between two common mutations C677T and A1298C in human methylenetetrahydrofolate reductase gene and the risk for diabetic nephropathy in type II diabetic patients. J Nutr. 2000; 130(10): 2493-7[PubMed]
  • 7. Dekou V, Whincup P, Papacosta O, Ebrahim S, Lennon L, Ueland PM, et al. The effect of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British regional heart study. Atherosclerosis. 2001; 154(3): 659-66
  • 8. Reardon MF, Nestel PJ, Craig IH, Harper RW. Lipoprotein predictors of the severity of coronary artery disease in men and women. Circulation. 1985; 71(5): 881-8[PubMed]
  • 9. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000; 101(16): 1899-906[PubMed]
  • 10. Clarke S, Banfield K, Carmel R, Jacobsen DW. Homocysteine in health and disease. 2001;
  • 11. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10(1): 111-3[DOI][PubMed]
  • 12. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998; 64(3): 169-72
  • 13. Kadziela J, Janas J, Dzielinska Z, Szperl M, Gazdzik D, Chotkowska E, et al. The C677T mutation in methylenetetrahydrofolate reductase gene, plasma homocysteine concentration and the risk of coronary artery disease. Kardiol Pol. 2003; 59(7): 17-26[PubMed]
  • 14. Rassoul F, Richter V, Hentschel B, Geisel J, Herrmann W, Kuntze T. Plasma homocysteine levels & 677C-->T methylenetetrahydrofolate reductase gene polymorphism in patients with coronary artery disease of different severity. Indian J Med Res. 2008; 127(2): 154-8[PubMed]
  • 15. Tokgozoglu SL, Alikasifoglu M, Atalar E, Aytemir K, Ozer N, et al. Methylene tetrahydrofolate reductase genotype and the risk and extent of coronary artery disease in a population with low plasma folate. Heart. 1999; 81(5): 518-22[PubMed]
  • 16. Heidari MM, Khatami M, Hadadzadeh M, Kazemi M, Mahamed S, Malekzadeh P, et al. Polymorphisms in NOS3, MTHFR, APOB and TNF-alpha Genes and Risk of Coronary Atherosclerotic Lesions in Iranian Patients. Res Cardiovasc Med. 2016; 5(1)[DOI][PubMed]
  • 17. Gu Y, Liu Z, Li L, Guo CY, Li CJ, Wang LS, et al. OLR1, PON1 and MTHFR gene polymorphisms, conventional risk factors and the severity of coronary atherosclerosis in a Chinese Han population. Cell Physiol Biochem. 2013; 31(1): 143-52[DOI][PubMed]
  • 18. Girelli D, Friso S, Trabetti E, Olivieri O, Russo C, Pessotto R, et al. Methylenetetrahydrofolate reductase C677T mutation, plasma homocysteine, and folate in subjects from northern Italy with or without angiographically documented severe coronary atherosclerotic disease: evidence for an important genetic-environmental interaction. Blood. 1998; 91(11): 4158-63[PubMed]
  • 19. Senemar S, Saffari B, Sharifkazemi MB, Bahari M, Jooyan N, Dehaghani ED, et al. 5,10-methylene tetrahydrofolate reductase C677T gene polymorphism, homocysteine concentration and the extent of premature coronary artery disease in southern Iran. EXCLI J. 2013; 12: 437-48[PubMed]
  • 20. Biselli PM, Guerzoni AR, Goloni-Bertollo EM, Godoy MF, Abou-Chahla JA, Pavarino-Bertelli EC. [MTHFR genetic variability on coronary artery disease development]. Rev Assoc Med Bras. 2009; 55(3): 274-8[PubMed]
  • 21. Lima LM, Carvalho M, Fernandes AP, Sabino Ade P, Loures-Vale AA, da Fonseca Neto CP, et al. Homocysteine and methylenetetrahydrofolate reductase in subjects undergoing coronary angiography. Arq Bras Cardiol. 2007; 88(2): 167-72[PubMed]
  • 22. Freitas AI, Mendonca I, Guerra G, Brion M, Reis RP, Carracedo A, et al. Methylenetetrahydrofolate reductase gene, homocysteine and coronary artery disease: the A1298C polymorphism does matter. Inferences from a case study (Madeira, Portugal). Thromb Res. 2008; 122(5): 648-56[DOI][PubMed]
  • 23. Yenilmez ED, Tuli A, Bozkurt A. The effects of factor V leiden, prothrombin G20210A, MTHFR C677T, MTHFR A1298C, factor XIIIA Val34Leu, factor XIIIB His95Arg and apolipoprotein E genotypes on coronary artery disease. 2012;
  • 24. Rothenbacher D, Fischer HG, Hoffmeister A, Hoffmann MM, Marz W, Bode G, et al. Homocysteine and methylenetetrahydrofolate reductase genotype: association with risk of coronary heart disease and relation to inflammatory, hemostatic, and lipid parameters. Atherosclerosis. 2002; 162(1): 193-200[PubMed]
  • 25. Kerkeni M, Addad F, Chauffert M, Myara A, Gerhardt M, Chevenne D, et al. Hyperhomocysteinaemia, methylenetetrahydrofolate reductase polymorphism and risk of coronary artery disease. Ann Clin Biochem. 2006; 43: 200-6[DOI][PubMed]
  • 26. Kolling K, Ndrepepa G, Koch W, Braun S, Mehilli J, Schomig A, et al. Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms, plasma homocysteine, folate, and vitamin B12 levels and the extent of coronary artery disease. Am J Cardiol. 2004; 93(10): 1201-6[DOI][PubMed]
  • 27. El-Sammak M, Kandil M, El-Hifni S, Hosni R, Ragab M. Elevated plasma homocysteine is positively associated with age independent of C677T mutation of the methylenetetrahydrofolate reductase gene in selected Egyptian subjects. Int J Med Sci. 2004; 1(3): 181-92[PubMed]
  • 28. Gasparovic J, Raslova K, Basistova Z, Zacharova M, Wsolova L, Avdicova M, et al. Effect of C677T methylenetetrahydrofolate reductase gene polymorphism on plasma homocysteine levels in ethnic groups. Physiol Res. 2004; 53(2): 215-8[PubMed]
  • 29. Russo GT, Friso S, Jacques PF, Rogers G, Cucinotta D, Wilson PW, et al. Age and gender affect the relation between methylenetetrahydrofolate reductase C677T genotype and fasting plasma homocysteine concentrations in the Framingham Offspring Study Cohort. J Nutr. 2003; 133(11): 3416-21[PubMed]
  • 30. Spotila LD, Jacques PF, Berger PB, Ballman KV, Ellison RC, Rozen R. Age dependence of the influence of methylenetetrahydrofolate reductase genotype on plasma homocysteine level. Am J Epidemiol. 2003; 158(9): 871-7[PubMed]
  • 31. Goyette P, Rozen R. The thermolabile variant 677C [arrow right] T can further reduce activity when expressed in CIS with severe mutations for human methylenetetrahydrofolate reductase. Hum. Mutat. 2000; 16(2): 132
  • 32. Hou X, Chen X, Shi J. Genetic polymorphism of MTHFR C677T and premature coronary artery disease susceptibility: A meta-analysis. Gene. 2015; 565(1): 39-44[DOI][PubMed]
  • 33. Matam K, Khan IA, Hasan Q, Rao P. Coronary artery disease and the frequencies of MTHFR and PON1 gene polymorphism studies in a varied population of Hyderabad, Telangana region in south India. J KING SAUD UNIV SCI . 2015; 27(2): 143-50
  • 34. Ramkaran P, Phulukdaree A, Khan S, Moodley D, Chuturgoon AA. Methylenetetrahydrofolate reductase C677T polymorphism is associated with increased risk of coronary artery disease in young South African Indians. Gene. 2015; 571(1): 28-32[DOI][PubMed]
  • 35. Senol S, Es MU, Gokmen G, Ercin O, Tuylu BA, Kargun K. Genetic polymorphisms in preoperative myocardial infarction. Asian Cardiovasc Thorac Ann. 2015; 23(4): 389-93[DOI][PubMed]
  • 36. Varga EA, Sturm AC, Misita CP, Moll S. Cardiology patient pages. Homocysteine and MTHFR mutations: relation to thrombosis and coronary artery disease. Circulation. 2005; 111(19)-93[DOI][PubMed]
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