Methylenetetrahydrofolate Reductase C677T and Platelet Glycoprotein IIb/IIIa Genes Polymorphism in Myocardial Infarction Egyptian Patients in Ismailia City

Kefah H Ali¹, Nagwan A Sabek^1, , Loaa A Tag Eldeen¹, Emad F Ismail¹ and Gamela Nasr²

¹Medical Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia, Egyp

²Cardiology Departments, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

Cite this paper:
Kefah H Ali, Nagwan A Sabek, Loaa A Tag Eldeen, Emad F Ismail and Gamela Nasr. Methylenetetrahydrofolate Reductase C677T and Platelet Glycoprotein IIb/IIIa Genes Polymorphism in Myocardial Infarction Egyptian Patients in Ismailia City. American Journal of Biomedical Research. 2016; 4(3):74-79. doi: 10.12691/ajbr-4-3-3

Abstract

Background: Hyperhomocysteinemia and platelet glycoprotein GpIIIa polymorphism had been identified as risk factors for coronary atherosclerosis. The methylenetetrahydrofolate reductase MTHFR C677T variant has been shown to influence homocysteine metabolism, the interaction of plasma tHcy with other conventional risk factors remain uncertain in the clinical setting of acute myocardial infarction (AMI). The present study aimed to examine whether the MTHFR and platelet glycoprotein IIIa polymorphisms were associated with increased risk of (MI) in Egyptian patients. Subjects and Method: 150 newly diagnosed MI patients and 50 healthy matched subjects were recruited into this study, genotyping of the MTHFR C677T and GpIIIa 1565 A¹/A² polymorphisms were carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, plasma tHcy, and folic acid levels were estimated. Results: Fasting plasma total Hcy levels were significantly higher in MI patients than controls (P <0.05), folate levels were significantly lower in MI patients than controls (P <0.05), no significant differences were observed in the MTHFR C677T and GpIIIa genotypes frequencies between MI patients and controls (P > 0.05). The frequency of the MTHFR C allele was 80.6 % and 76 % in MI patients and controls respectively and did not differ significantly between the two groups (P > 0.05). The frequency of risk allele, GpIIIa, PIA² was significantly higher in MI patients compared to controls (p<0.05), plasma tHcy level was significantly higher and folate level was significantly lower in MI patients carrying MTHFR CC and GPIIIa PIA²A²genotypes. Conclusions: In this population, the both risk alleles of MTHFR and GpIIb/IIIa polymorphisms had no major effect on the MI incidence, they were associated with higher homocysteine levels. A gene-environment interaction might increase the risk indirectly by elevating tHcy, especially when folate intake was low, our findings might support that MTHFR and GpIIb/IIIa polymorphisms as risk factors for MI.

Keywords:
Myocardial infarction (MI) homocysteine (tHcy) folate methylenetetrahydrofolate reductase (MTHFR) Glycoprotein (GP) IIb/IIIa

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	WHO, 2014; http://www.worldlifeexpectancy.com/egypt-coronary-heart-disease.
[2]	WHO and ARE-Ministry of Health & Population: Egypt National Stepwise Survey of on Communicable Diseases Risk Factors 2011-2012.
[3]	Smith SC. Current and future directions of cardiovascular risk prediction. Am J Cardiol. 2006 Jan 16;97(2A):28A-32A.
[4]	Towfighi A, Saver JL, Engelhardt R, Ovbiagele B: Factors associated with the steep increase in late-midlife stroke occurrence among US men. J Stroke Cerebrovasc Dis (2008)17(4):165-168.
[5]	Beard RS, Bearden SE: Vascular complications of cystathionine β-synthase deficiency: Future directions for homocysteine-to-hydrogen sulfide research. Am J Physiol Heart Circ Physiol (2011) 300(1):H13-H26.
[6]	William P. Homocysteine and thrombosis: guilt by association? Blood; 2012 119: 2977-2978.
[7]	Holmes MV, Newcombe P, Hubacek JA: Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomized trials. Lancet 2011; 378:584-594.
[8]	Frosst P, Blom MJ, Lios R, Goyette P, Sheppard CA, Matthews RG. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111-113.
[9]	Furie B, Furie BC. Mechanisms of Thrombus Formation. N Engl J Med. 2008; 359:938-49.
[10]	Ruggeri ZM, Mendolicchio GL. Adhesion Mechanisms in Platelet Function. Circ Res. 2007; 100:1673-85.
[11]	Bennett JS. Structure and function of the platelet integrin alphaIIbeta3. J Clin Invest. 2005; 115:3363-9.
[12]	Carter AM, Catto AJ, Bamford JM, Grant JP. Association of the platelet glycoprotein IIb HPA-3 polymorphism with survival after acute ischemic stroke. Stroke. 1999;30:2606-11.
[13]	Newman PJ, Derbes R, Aster RH. The human platelet alloantigens, PI A1 and PI 2, are associated with a leucine33/proline 33 amino acid polymorphism in membrane glycoprotein IIIa and are distinguishable by DNA typing. J Clin Invest 1989;83:1778-1781.
[14]	European Society of Cardiology. Management of stable angina pectoris. Recommendations of the Task Force of the European Society of Cardiology. Eur Heart J 1997;18: 394-413.
[15]	Bong Su, Dae Ho, Nam K, Jong W: Relationship between Metabolic Syndrome and MTHFR Polymorphism in Colorectal Cancer. J Korean Soc Coloproctol 2011:27(2); 78-82.
[16]	Giuseppe A, Pietro M, Pietro S, defective platelet response to arachidonic acid and thromboxane A2 in subjects with PlA2 polymorphism of b3 subunit (glycoprotein IIIa) British Journal of Haematology, 2000, 110, 911-918.
[17]	Selhub J, Morris M, Jacques P. In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations. Proc Natl Acad Sci USA 2007; 104:1995-20000.
[18]	Trinder. P. Determination of blood glucose using an oxidase – peroxidase system with a noncarcinogenic chromogen. Journal of clinical pathology, 1969;19692: 158-161
[19]	Alian. C., Poon. L. and Chan. C. Enzymatic determination of total serum cholesterol. CLIN. CHEM.., 1974; 20 (4): 470-475.
[20]	Siedel. J., Schmuck. R. and Staepels. J. Long-term stable liquid ready to use mono-reagent for the enzymatic assay of serum or plasma triglycerides (GPO-PAP method). AACC Meeting. Abstract 34. Clin Chem., 1993; 39: 1127.
[21]	Lopes-Virella M., Stone R., Ellis S. and Colwell J. Cholesterol determination in high-density lipoproteins separated by three different methods. Clin Chem., 1977; 23:882-884.
[22]	Marniemi J, Maki J, Maatela J, Poor applicability of the Friedewald formula in the assessment of serum LDL cholesterol for clinical purposes. Clin Biochem. 1995; 28(3):285-289.
[23]	Cattaneo M. Hyperhomocysteinemia, atherosclerosis, and thrombosis. Thromb Haemost. 1999; 81:165-76.
[24]	Chua S, Wu CJ, Chang HW, Hang CL, Chen CJ, Yang CH, Impact of elevated plasma total homocysteine concentration on coronary atherosclerosis in Chinese patients with acute myocardial infarction undergoing primary coronary intervention. Int Heart J. 2005; 46: 181-193.
[25]	Pandey U, Kumari R, Nath B. Association of angiotensin- converting enzyme, Methylenetetrahydrofolate reductase and paraoxonase gene polymorphism and coronary artery disease in an Indian Cardiol J. 2011; 18(4):385-394.
[26]	Kuo HK, Sorond FA, Chen JH. The role of homocysteine in multisystem age-related problems: a systematic review. J Gerontol A Biol Sci Med Sci 2005;60:1190-201.
[27]	Jing Ma, Meir J, Charles H. Methylenetetrahydrofolate Reductase Polymorphism, Plasma Folate, Homocysteine, and Risk of Myocardial Infarction in US Physicians Circulation. 1996; 94: 2410-2416.
[28]	Jacques PF, Bostom AG, Williams RR. The relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation. 1996;93:7-9.
[29]	Liang R, Zhou Y, Xie J. Association of C677T gene polymorphisms of methylenetetrahydrofolate reductase and plasma homocysteine level with hyperlipidemia. Nan Fang Yi Ke Da Xue Xue Bao. 2014 Jul;34(8):1195.
[30]	Andreassi MG, Botto N, Cocci F. Methylenetetrahydrofolate': reductase gene C677 T polymorphism, homocysteine, vitamin 8121 folic -acid and DNA damage in coronary artery disease. Hum Genet 2003; 112(2):171-177.
[31]	Qyang B, Fan S, Zhi X, Li Y. Associations of MTHFR Gene Polymorphisms with Hypertension and Hypertension in Pregnancy: A Meta- Analysis from 114 Studies with 15411 Cases and 21970 Controls. PLoS ONE. 2014; 9 (2):e87497.
[32]	Wu Y, Tomon M, Sumino K. Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke: sex difference in Japanese. Kobe J Med Sci 2001; 47:255-262.
[33]	Zheng Y, Tong J, Do X. Prevalence of methylenetetrahydrofolate reductase C677T and its association with arterial and venous thrombosis in the Chinese population. Br J Haematol 2000; 109: 870-874.
[34]	Weiss EJ, Bray PF, Tayback M. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. New Engl J Med 1996;334:1090-1094.
[35]	Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F, Sabate M, Fernandez C, PlA polymorphism and platelet reactivity following clopidogrel loading dose in patients undergoing coronary stent implantation. Blood Coagul Fibrinolysis 2004; 15: 89-93.
[36]	Duan H, Cai Y, and Sun X. Platelet glycoprotein IIb/IIIa polymorphism HPA-3 b/b is associated with increased risk of ischemic stroke in patients under 60 years of age Med Sci Monit. 2012; 18(1).
[37]	Roberta di, Emma M, Matteo N. Hydrogen sulfide pathway contributes to the enhanced human platelet aggregation in hyperhomocysteinemia. PNAS. 2013;110 no. 39:15812-15817.