Incidence of the genetic mutations in patients with coronary artery disease

Yıl 2017, Cilt: 3 Sayı: 2, 145 - 151, 04.07.2017

Meral Ekim , Hasan Ekim

https://doi.org/10.18621/eurj.286198

Cited By: 1

Öz

Objectives. Coronary artery disease (CAD) is the leading cause of
mortality in the world. It is a complex disorder resulting from the interaction
between environmental risk factors and hereditary predisposition. The role of
the factor V Leiden (FVL), protrombin gene (PT G20210A) and methylenetetrahydrofolate
reductase (MTHFR) C677T polymorphisms in the development of CAD is
controversial. In this study, we investigated the incidence of these polymorphisms
in order to delineate their roles in the development of CAD in a tertiary
University hospital. Methods. This study included 58
consecutive CAD patients. Diabetic and hypertensive patients were excluded.
FVL, PT G20210A, and MTHFR (C677T, A1298C) mutations were investigated in all
patients. Polymerase chain reaction and the amplification refractory mutation
system were used to identify these polymorphisms. Results. Thirty-six men
and 22 women were enrolled with an age ranging between 41 to 85 (mean age: 62.75±9.18 years). The heterozygous PT G20210A genotype was
identified in 5 (8.6%) patients (2 males, 3 females). The heterozygous FVL
genotype was found in 8 (13.8%) patients (6 males and 2 females). The incidence
of homozygous MTHFR C677T and homozygous MTHFR A1298 carriers was found to be
17.2% and 8.6%, respectively. There were no significant differences in the
distribution of polymorphisms according to gender (p>0.05). Conclusions. The FVL and PT G20210A
polymorphisms most likely play a contributory role in the development of CAD.
In contrast, the MTHFR C677T and MTHFR A1298C genotypes were not associated
with a predisposition to the development of CAD. However, in compound MTHFR
C677T/A1298C carriers, the presence of FVL or PT G20210 polymorphism may
contribute the development of CAD. Further studies are needed to support these
findings. 

Anahtar Kelimeler

Methylenetetrahydrofolate reductase, polymorphism, genetic mutation, atherosclerosis, coronary artery disease

Kaynakça

• [1] Ciftdogan DY, Coskun S, Ulman C, Tikiz H. The Factor V G1691A, Factor V H1299R, prothrombin G 20210A polymorphisms in children with family history of premature coronary artery disease. Coron Artery Dis 2009;20:435-9.
• [2] Ercan B, Tamer L, Sucu N, Pekdemir H, Camsari A, Atik U. Factor V Leiden and prothrombin G20210A gene polymorphisms in patients with coronary artery disease. Yonsei Med J 2008;49:237-43.
• [3] Hobikoglu GF, Akyuz U, Akyuz F, Ozer O, Guney D, Narin A, et al. Factor V Leiden is a risk factor for myocardial infarction in young Turkish men. Acta Cardiol 2004;59:594-7.
• [4] Donmez Y, Kanadasi M, Tanriverdi K, Demir M, Demirtas M, Cayli M, et al. Prothrombin G20210A and factor V Leiden mutations in patients less than 55 years old with myocardial infarction. Jpn Heart J 2004;45:505-12.
• [5] Rahimi Z, Nomani H, Mozafari H, Vaisi-Raygani A, Madani H, Malek-Khosravi S, et al. Factor V G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase polymorphism C677T are not associated with coronary artery disease and type 2 diabetes mellitus in Western Iran. Blood Coagul Fibrinolysis 2009;20:252-6.
• [6] Eskandari MK, Bontempo FA, Hassett AC, Faruki H, Makaroun MS. Arterial thromboemblic events in patients with the factor V Leiden mutation. Am J Surg 1998;176:122-5.
• [7] Poort SR, Rosendaal FR, Reitsma PH, and Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996;88:3698-703.
• [8] Hotoleanu C, Trifa A, Popp R, Fodor D. The importance of homozygous polymorphisms of methylenetetrahydrofolate reductase gene in Romanian patients with idiopathic venous thromboembolism. Balkan Med J 2013;30:197-203.
• [9] Gurlertop HY, Gundogdu F, Pirim I, Islamoglu Y, Egerci N, Sevimli S, et al. Association between factor V Leiden mutation and coronary artery disease in the northeast region of Turkey. Blood Coagul Fibrinolysis 2007;18:719-22.
• [10] Rosendaal FR, Siscovick DS, Schwartz SM, Psaty BM, Raghunathan TE, Vus HL. A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood 1997;90:1747-50.
• [11] Boroumand M, Pourgholi L, Ziaee S, Anvari MS, Jalali A, Goodarzynejad H. The association between Factor V Leiden with the presence and severity of coronary artery disease. Clin Biochem 2014;47:356-60.
• [12] Dunn ST, Courtney R, Schechter E, Moore WE, Lee ET, Eichner JE. Role of Factor V Leiden mutation in patients with angiographically demonstrated coronary artery disease. Thromb Res 1998;91:91-9.
• [13] Emiroglu O, Durdu S, Egin Y, Akar AR, Alakoc YD, Zaim C, et al. Thrombotic gene polymorphisms and postoperative outcome after coronary artery bypass graft surgery. J Cardiothorac Surg 2011;6:120.
• [14] Akar N. Factor V 1691 G-A mutation distribution in a healthy Turkish population. Turk J Hematol 2009;26:9-11.
• [15] Donahue BS, Gailani D, Higgins MS, Drinkwater DC, George AL, Jr. Factor V Leiden protects against blood loss and transfusion after cardiac surgery. Circulation 2003;107:1003-8.
• [16] Massoudy P, Thielmann M, Muller-Beissenhirtz H, Gorlinger K, Dietrich W, Herget-Rosenthal S, et al. Thrombophilia in cardiac surgery-patients with symptomatic factor V Leiden. J Card Surg 2009;24:379-82.
• [17] Franco RF, Trip MD, ten Cate H, van den Ende A, Prins MH, Kastelein JJ, et al. The 20210 GA mutation in the 3’-untranslated region of the prothrombin gene and the risk for arterial thrombotic disease. Br J Haematol 1999;104:50-4.
• [18] Jadaon MM. Epidemiology of prothrombin G20210A mutation in the Mediterranean region. Mediterr J Hematol Infect Dis 2011;3:e2011054.
• [19] Russo C, Girelli D, Olivieri O, Guarini P, Manzato F, Pizzolo F, et al. G20210A prothrombin gene polymorphism and prothrombin activity in subjects with or without angiographically documented coronary artery disease. Circulation 2001;103:2436-40.
• [20] Gulec S, Aras O, Akar E, Tutar E, Omurlu K, Avci F, et al. Methylenetetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction. Clin Cardiol 2001;24:281-4.
• [21] Han TW, Zhou SS, Li JT, Tian F, Mu Y, Jing J, et al. Homocysteine is associated with the progression of non-culprit coronary lesions in elderly acute coronary syndrome patients after percutaneous coronary intervention. J Geriatr Cardiol 2016;13:299-305.
• [22] Yilmaz H, Isbir S, Agachan B, Ergen A, Farsak B, Isbir T. C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease. Cell Biochem Funct 2006;24:87-90.
• [23] Rady PL, Tyring SK, Hudnall SD, Vargas T, Kellner LH, Nitowsky H, et al. Methylenetetrahydrofolate reductase (MTHFR): The incidence of mutations C677T and A1298C in the Ashkenazi Jewish population. Am J Med Genet 1999;86:380-84.
• [24] Sazci A, Ergul E, Kaya G, Kara I. Genotype and allele frequencies of the polymorphic methylenetetrahydrofolate reductase gene in Turkey. Cell Biochemm Funct 2005;23:51-4.
• [25] Botto N, Andreassi MG, Rizza A, Berti S, Bevilacqua S, Federici C, et al. C677T polymorphism of the methylenetetrahydrofolate reductase gene is a risk factor of adverse events after coronary revascularization. Int J Cardiol 2004;96:341-5.
• [26] Yenilmez ED, Tuli A, Bozkurt A, Acarturk E. 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. Turk J Biochem 2012;37:424-30.
• [27] Kalina A, Czeizel AE. The methylenetetrahydrofolate reductase gene polymorphism (C677T) is associated with increased cardiovascular mortality in Hungary. Int J Cardiol 2004;97:333-4.
• [28] Gupta SK, Kotwal J, Kotwal A, Dhal A, Garg S. Role of homosysteine & MTHFR C677T gene polymorphism as risk factors for coronary artery disease in young Indians. Indian J Med Res 2012;135;506-12.
• [29] Kawashiri M, Kajinami K, Nohara A, Yagi K, Inazu A, Koizumi J, et al. Effect of common methylenetetrahydrofolate reductase gene mutation on coronary artery disease in familial hypercholesterolemia. Am J Cardiol 2000;86:840-5.
• [30] Kim CH, Hwang KY, Choi TM, Shin WY, Hong SY. The methylenetetrahydrofolate reductase gene polymorphism in Koreans with coronary artery disease. Int J Cardiol 2001;78:13-7.
• [31] Jee SH, Beaty TH, Suh I, Yoon YS, Appel LJ. The methylenetetrahydrofolate reductase gene is associated with increased cardiovascular risk in Japan, but not in other populations. Atherosclerosis 2000;153:161-8.