Prothrombin Gene G20210A Variant in Angiographically Documented Patients with Coronary Artery Stenosis
-
Leyla Pourgholi
,
Hamidreza Goodarzynejad
,
Shayan Ziaee
,
Elmira Zare
,
Arash Jalali
,
Mohammadali Boroumand
Abstract
Background: Studies on the association between the prothrombin G20210A variant and coronary artery disease (CAD) risk are inconclusive. This study aimed to investigate the possible association between the G20210A variant in the prothrombin gene and documented CAD and its severity.
Methods: This study enrolled 1460 patients who were consecutively admitted for elective coronary angiography. Via the standard angiographic techniques, coronary angiographies were done and the presence and severity of CAD were determined through the clinical vessel score and the Gensini score. Prothrombin G20210A genotypes were identified using PCR-RFLP.
Results: This cross-sectional study was performed on 953 men and 507 women at a mean age of 58.21±10.33 years. The median and the interquartile range for the Gensini score were not statistically significantly different between the wild (GG) and mutant (AA+GA) genotypes (P=0.440). The association between the G20210A polymorphism and the severity of CAD with respect to the vessel score also showed no significant linear trend of higher numbers of diseased vessels (P= 0.765 for the Mantel–Haenszel test of linear trend) in the AA+GA genotype as compared with the GG genotype.
Conclusion: Our data failed to confirm the hypothesis that the G20210A variant mutation may be a significant determinant of CAD risk or its severity.
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2. Poort SR, Rosendaal FR, Reitsma PH, 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;88:3698-3703.
3. Jin B, Li Y, Ge-Shang QZ, Ni HC, Shi HM, Shen W. Varied association of prothrombin G20210A polymorphism with coronary artery disease susceptibility in different ethnic groups: evidence from 15,041 cases and 21,507 controls. Mol Biol Rep 2011;38:2371-2376.
4. Roberts R. Genetics of premature myocardial infarction. Curr Atheroscler Rep 2008;10:186-193.
5. Burzotta F, Paciaroni K, De Stefano V, Chiusolo P, Manzoli A, Casorelli I, Leone AM, Rossi E, Leone G, Maseri A, Andreotti F. Increased prevalence of the G20210A prothrombin gene variant in acute coronary syndromes without metabolic or acquired risk factors or with limited extent of disease. Eur Heart J 2002;23:26-30.
6. Abu-Amero KK1, Wyngaard CA, Kambouris M, Dzimiri N. Prevalence of the 20210 G-->A prothrombin variant and its association with coronary artery disease in a Middle Eastern Arab population. Arch Pathol Lab Med 2002;126:1087-1090.
7. Gundogdu F, Gurlertop Y, Pirim I, Arslan S, Ikbal M, Islamoglu Y, Aksoy H, Senocak H. G20210A Prothrombin gene variant in Turkish patients with angiographically documented coronary artery disease. J Thromb Thrombolysis 2007;24:255-259.
8. 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;49:237-243.
9. Rahimi Z, Nomani H, Mozafari H, Vaisi-Raygani A, Madani H, Malek-Khosravi S, Parsian A. 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;20:252-256.
10. Almawi WY, Ameen G, Tamim H, Finan RR, Irani-Hakime N. Factor V G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677T gene polymorphism in angiographically documented coronary artery disease. J Thromb Thrombolysis 2004;17:199-205.
11. Gardemann A, Arsic T, Katz N, Tillmanns H, Hehrlein FW, Haberbosch W. The factor II G20210A and factor V G1691A gene transitions and coronary heart disease. Thromb Haemost 1999;81:208-213.
12. Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 1983;51:606.
13. Boroumand M, Ghaedi M, Mohammadtaghvaei N, Pourgholi L, Anvari MS, Davoodi G, Amirzadegan A, Saadat S, Sheikhfathollahi M, Goodarzynejad H. Association of estrogen receptor alpha gene polymorphism with the presence of coronary artery disease documented by coronary angiography. Clin Biochem 2009;42:835-839.
14. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
15. Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta N, Steer BM, Ingram AJ, Gupta M, Al-Omran M, Teoh H, Marsden PA, Verma S. MicroRNA-145 targeted therapy reduces atherosclerosis. Circulation 2012;126(11 Suppl 1):S81-90.
16. Mazoyer E, Ripoll L, Gueguen R, Tiret L, Collet JP, dit Sollier CB, Roussi J, Drouet L; FITENAT Study Group. Prevalence of factor V Leiden and prothrombin G20210A mutation in a large French population selected for nonthrombotic history: geographical and age distribution. Blood Coagul Fibrinolysis 2009;20:503-510.
17. Folsom AR, Cushman M, Tsai MY, Heckbert SR, Aleksic N. Prospective study of the G20210A polymorphism in the prothrombin gene, plasma prothrombin concentration, and incidence of venous thromboembolism. Am J Hematol 2002;71:285-290.
18. Brown K, Luddington R, Williamson D, Baker P, Baglin T. Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 3'-untranslated region of the prothrombin gene. Br J Haematol 1997;98:907-909.
19. Russo C, Girelli D, Olivieri O, Guarini P, Manzato F, Pizzolo F, Zaia B, Mazzucco A, Corrocher R. G20210A prothrombin gene polymorphism and prothrombin activity in subjects with or without angiographically documented coronary artery disease. Circulation 2001;103:2436-2440.
20. Miller GJ, Bauer KA, Barzegar S, Cooper JA, Rosenberg RD. Increased activation of the haemostatic system in men at high risk of fatal coronary heart disease. Thromb Haemost 1996;75:767-771.
21. Forte GI, Vaccarino L, Palmeri M, Branzi A, Caldarera CM, Scola L, Caruso C, Licastro F, Lio D. Analysis of polymorphisms Leiden Factor V G1691A and prothrombin G20210A as risk factors for acute myocardial infarction. Biogerontology 2011;12:485-490.
22. Berredjeb Ben Slama D, Fekih-Mrissa N, Haggui A, Nsiri B, Baraket N, Haouala H, Gritli N. Lack of association between factor V Leiden and prothrombin G20210A polymorphisms in Tunisian subjects with a history of myocardial infarction. Cardiovasc Pathol 2013;22:39-41.
23. Tomaiuolo R, Bellia C, Caruso A, Di Fiore R, Quaranta S, Noto D, Cefalù AB, Di Micco P, Zarrilli F, Castaldo G, Averna MR, Ciaccio M. Prothrombotic gene variants as risk factors of acute myocardial infarction in young women. J Transl Med 2012;10:235.
24. Zöller B. Low degree of shared genetic susceptibility to coronary artery disease and venous thromboembolism. Thromb Res 2014;134:219-220.
25. Rosendaal FR, Siscovick DS, Schwartz SM, Psaty BM, Raghunathan TE, Vos HL. A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood 1997;90:1747-1750.
26. Doggen CJ, Cats VM, Bertina RM, Rosendaal FR. Interaction of coagulation defects and cardiovascular risk factors: increased risk of myocardial infarction associated with factor V Leiden or prothrombin 20210A. Circulation 1998;97:1037-1041.
27. Alkhiary W, Azzam H, Yossof MM, Aref S, Othman M, El-Sharawy S. Association of hemostatic gene polymorphisms with early-onset ischemic heart disease in Egyptian patients. Clin Appl Thromb Hemost 2016;22:535-542.
28. Segev A, Ellis MH, Segev F, Friedman Z, Reshef T, Sparkes JD, Tetro J, Pauzner H, David D. High prevalence of thrombophilia among young patients with myocardial infarction and few conventional risk factors. Int J Cardiol 2005;98:421-424.
29. Ye Z, Liu EH, Higgins JP, Keavney BD, Lowe GD, Collins R, Danesh J. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 2006;367:651-658.
30. Kim RJ, Becker RC. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. Am Heart J 2003;146:948-957.
31. Ridker PM, Hennekens CH, Miletich JP. G20210A mutation in prothrombin gene and risk of myocardial infarction, stroke, and venous thrombosis in a large cohort of US men. Circulation 1999;99:999-1004.
32. Rosendaal FR, Doggen CJ, Zivelin A, Arruda VR, Aiach M, Siscovick DS, Hillarp A, Watzke HH, Bernardi F, Cumming AM, Preston FE, Reitsma PH. Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost 1998;79:706-708.
33. Lander ES, Schork NJ. Genetic dissection of complex traits. Science 1994;265:2037-2048.
34. Burzotta F, Paciaroni K, De Stefano V, Crea F, Maseri A, Leone G, Andreotti F. G20210A prothrombin gene polymorphism and coronary ischaemic syndromes: a phenotype-specific meta-analysis of 12 034 subjects. Heart 2004;90:82-86.
2. Poort SR, Rosendaal FR, Reitsma PH, 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;88:3698-3703.
3. Jin B, Li Y, Ge-Shang QZ, Ni HC, Shi HM, Shen W. Varied association of prothrombin G20210A polymorphism with coronary artery disease susceptibility in different ethnic groups: evidence from 15,041 cases and 21,507 controls. Mol Biol Rep 2011;38:2371-2376.
4. Roberts R. Genetics of premature myocardial infarction. Curr Atheroscler Rep 2008;10:186-193.
5. Burzotta F, Paciaroni K, De Stefano V, Chiusolo P, Manzoli A, Casorelli I, Leone AM, Rossi E, Leone G, Maseri A, Andreotti F. Increased prevalence of the G20210A prothrombin gene variant in acute coronary syndromes without metabolic or acquired risk factors or with limited extent of disease. Eur Heart J 2002;23:26-30.
6. Abu-Amero KK1, Wyngaard CA, Kambouris M, Dzimiri N. Prevalence of the 20210 G-->A prothrombin variant and its association with coronary artery disease in a Middle Eastern Arab population. Arch Pathol Lab Med 2002;126:1087-1090.
7. Gundogdu F, Gurlertop Y, Pirim I, Arslan S, Ikbal M, Islamoglu Y, Aksoy H, Senocak H. G20210A Prothrombin gene variant in Turkish patients with angiographically documented coronary artery disease. J Thromb Thrombolysis 2007;24:255-259.
8. 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;49:237-243.
9. Rahimi Z, Nomani H, Mozafari H, Vaisi-Raygani A, Madani H, Malek-Khosravi S, Parsian A. 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;20:252-256.
10. Almawi WY, Ameen G, Tamim H, Finan RR, Irani-Hakime N. Factor V G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677T gene polymorphism in angiographically documented coronary artery disease. J Thromb Thrombolysis 2004;17:199-205.
11. Gardemann A, Arsic T, Katz N, Tillmanns H, Hehrlein FW, Haberbosch W. The factor II G20210A and factor V G1691A gene transitions and coronary heart disease. Thromb Haemost 1999;81:208-213.
12. Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 1983;51:606.
13. Boroumand M, Ghaedi M, Mohammadtaghvaei N, Pourgholi L, Anvari MS, Davoodi G, Amirzadegan A, Saadat S, Sheikhfathollahi M, Goodarzynejad H. Association of estrogen receptor alpha gene polymorphism with the presence of coronary artery disease documented by coronary angiography. Clin Biochem 2009;42:835-839.
14. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
15. Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta N, Steer BM, Ingram AJ, Gupta M, Al-Omran M, Teoh H, Marsden PA, Verma S. MicroRNA-145 targeted therapy reduces atherosclerosis. Circulation 2012;126(11 Suppl 1):S81-90.
16. Mazoyer E, Ripoll L, Gueguen R, Tiret L, Collet JP, dit Sollier CB, Roussi J, Drouet L; FITENAT Study Group. Prevalence of factor V Leiden and prothrombin G20210A mutation in a large French population selected for nonthrombotic history: geographical and age distribution. Blood Coagul Fibrinolysis 2009;20:503-510.
17. Folsom AR, Cushman M, Tsai MY, Heckbert SR, Aleksic N. Prospective study of the G20210A polymorphism in the prothrombin gene, plasma prothrombin concentration, and incidence of venous thromboembolism. Am J Hematol 2002;71:285-290.
18. Brown K, Luddington R, Williamson D, Baker P, Baglin T. Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 3'-untranslated region of the prothrombin gene. Br J Haematol 1997;98:907-909.
19. Russo C, Girelli D, Olivieri O, Guarini P, Manzato F, Pizzolo F, Zaia B, Mazzucco A, Corrocher R. G20210A prothrombin gene polymorphism and prothrombin activity in subjects with or without angiographically documented coronary artery disease. Circulation 2001;103:2436-2440.
20. Miller GJ, Bauer KA, Barzegar S, Cooper JA, Rosenberg RD. Increased activation of the haemostatic system in men at high risk of fatal coronary heart disease. Thromb Haemost 1996;75:767-771.
21. Forte GI, Vaccarino L, Palmeri M, Branzi A, Caldarera CM, Scola L, Caruso C, Licastro F, Lio D. Analysis of polymorphisms Leiden Factor V G1691A and prothrombin G20210A as risk factors for acute myocardial infarction. Biogerontology 2011;12:485-490.
22. Berredjeb Ben Slama D, Fekih-Mrissa N, Haggui A, Nsiri B, Baraket N, Haouala H, Gritli N. Lack of association between factor V Leiden and prothrombin G20210A polymorphisms in Tunisian subjects with a history of myocardial infarction. Cardiovasc Pathol 2013;22:39-41.
23. Tomaiuolo R, Bellia C, Caruso A, Di Fiore R, Quaranta S, Noto D, Cefalù AB, Di Micco P, Zarrilli F, Castaldo G, Averna MR, Ciaccio M. Prothrombotic gene variants as risk factors of acute myocardial infarction in young women. J Transl Med 2012;10:235.
24. Zöller B. Low degree of shared genetic susceptibility to coronary artery disease and venous thromboembolism. Thromb Res 2014;134:219-220.
25. Rosendaal FR, Siscovick DS, Schwartz SM, Psaty BM, Raghunathan TE, Vos HL. A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood 1997;90:1747-1750.
26. Doggen CJ, Cats VM, Bertina RM, Rosendaal FR. Interaction of coagulation defects and cardiovascular risk factors: increased risk of myocardial infarction associated with factor V Leiden or prothrombin 20210A. Circulation 1998;97:1037-1041.
27. Alkhiary W, Azzam H, Yossof MM, Aref S, Othman M, El-Sharawy S. Association of hemostatic gene polymorphisms with early-onset ischemic heart disease in Egyptian patients. Clin Appl Thromb Hemost 2016;22:535-542.
28. Segev A, Ellis MH, Segev F, Friedman Z, Reshef T, Sparkes JD, Tetro J, Pauzner H, David D. High prevalence of thrombophilia among young patients with myocardial infarction and few conventional risk factors. Int J Cardiol 2005;98:421-424.
29. Ye Z, Liu EH, Higgins JP, Keavney BD, Lowe GD, Collins R, Danesh J. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 2006;367:651-658.
30. Kim RJ, Becker RC. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. Am Heart J 2003;146:948-957.
31. Ridker PM, Hennekens CH, Miletich JP. G20210A mutation in prothrombin gene and risk of myocardial infarction, stroke, and venous thrombosis in a large cohort of US men. Circulation 1999;99:999-1004.
32. Rosendaal FR, Doggen CJ, Zivelin A, Arruda VR, Aiach M, Siscovick DS, Hillarp A, Watzke HH, Bernardi F, Cumming AM, Preston FE, Reitsma PH. Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost 1998;79:706-708.
33. Lander ES, Schork NJ. Genetic dissection of complex traits. Science 1994;265:2037-2048.
34. Burzotta F, Paciaroni K, De Stefano V, Crea F, Maseri A, Leone G, Andreotti F. G20210A prothrombin gene polymorphism and coronary ischaemic syndromes: a phenotype-specific meta-analysis of 12 034 subjects. Heart 2004;90:82-86.
| Files | ||
| Issue | Vol 14 No 4 (2019): J Teh Univ Heart Ctr | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/jthc.v14i4.1988 | |
| Keywords | ||
| Coronary artery disease Prothrombin; Coronary angiography Single-nucleotide polymorphism | ||
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How to Cite
1.
Pourgholi L, Goodarzynejad H, Ziaee S, Zare E, Jalali A, Boroumand M. Prothrombin Gene G20210A Variant in Angiographically Documented Patients with Coronary Artery Stenosis. J Tehran Heart Cent. 2019;14(4):150-155.
