Abstract
It is known from large epidemiological studies that the elevation of coagulation factor VII in plasma is an independent risk factor for acute coronary syndromes. The level of factor VII is influenced by polymorphic sites in the factor VII gene. However, data on the association of such polymorphisms with the risk of acute coronary syndromes are conflicting. A decanucleotide insertion/deletion polymorphic site has been described in the promoter of the factor VII gene that leads to a dramatic change in the plasma factor VII levels. We therefore analyzed the association of this polymorphism with the risk of acute coronary syndromes in a case-control study. Included in the study were 111 patients with angiographically documented acute coronary syndromes and 108 age- and sex-matched individuals from the same geographic area without signs or symptoms of coronary heart disease. The presence or absence of the decanucleotide stretch at position −323 in the promoter of factor VII was monitored using a polymerase chain reaction (PCR)–based restriction technique. The prevalence of the genotype with the homozygous deletion was similar in the patients with acute coronary syndromes (79.2%) and in the control patients (79.6%). There was a non-significant trend toward a higher prevalence of the homozygote deletion in patients with premature acute coronary syndromes (77.4%) compared with an age-matched subgroup of the control patients (67.5%) (odds ratio [OR] 1.6, confidence interval [CI] 0.95, 0.61–3.93). Thus, we could not find a significant association of the ocurrence of acute coronary events with the insertion/deletion polymorphism in factor VII.
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Meade TW, Mellows S, Brozovic M, et al. Haemostatic function in ischemic heart disease: Principle results of the Northwick Park Heart Study. Lancet 1986;2(8506): 533-537.
Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors and long-term incidence of ischaemic heart disease. Lancet 1993;342:1076-1079.
Heinrich J, Balleisen L, Schulte H, Assmann G, van de Loo J. Fibrinogen and factor VII in the prediction of coronary risk: Results from the PROCAM study in healthy men. Arterioscler Thromb 1994;14:54-59.
Folsom AR, Wu KK, Davis CE, Conlan MG, Sorlie PD, Szklo M. Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors. Atherosclerosis 1991,91:191-205.
van der Bom JG, de Maat MP, Bots ML, et al. Elevated plasma fibrinogen: Cause or consequence of cardiovascular disease? Arterioscler Thromb Vasc Biol 1998;18:621-625.
Scarabin PY, Bara L, Ricard S, et al. Genetic variation at the beta-fibrinogen locus in relation to plasma fibrinogen concentrations and risk of myocardial infarction. The ECTIM Study. Arterioscler Thromb 1993;13:886-891.
Hoffmann CJ, Lowson WE, Miller RH, Hultin MB. Correlation of vitamin K-dependent clotting factors with cholesterol and triglycerides in healthy young adults. Arterioscler Thromb 1994;14:191-205.
Heywood DM, Ossei-Gerning N, Grant PJ. Association of factor VII:C levels with environmental and genetic factors in patients with ischaemic heart disease and coronary atheroma characterised by angiography. Thromb Haemost 1996;76:161-165.
van der Bom JG, Bots ML, van Vliet HHDM, Hofman A, Grobbee DE. Factor VII coagulant activity is related to blood lipids in the elderly. The Rotterdam study. Fibrinolysis 1994;8:132-140.
Thomas AE, Green FR, Kelleher CH, et al. Variation in the promoter region of the beta fibrinogen gene is associated with plasma fibrinogen levels in smokers and non-smokers. Thromb Haemost 1991;65:487-490.
Tybjaerg-Hansen A, Agerholm-Larsen B, Humphries SE, Abildgaard S, Schnohr P, Nordestgaard BG. A common mutation (G-455 → A) in the beta-fibrinogen promoter is an independent predictor of plasma fibrinogen, but not of ischemic heart disease. A study of 9,127 individuals based on the Copenhagen City Heart Study. J Clin Invest 1997;99:3034-3039.
Watzke HH, Schüttrumpf J, Graf S, Huber K, Panzer S. Increased prevalence of a polymorphism in the gene coding for human prothrombin in patients with coronary heart disease. Thromb Res 1997;87:521-526.
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.
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.
Corral J, Gonzalez-Conejero R, Lozano ML, Rivera J, Heras I, Vicente V. The venous thrombosis risk factor 20210 A allele of the prothrombin gene is not a major risk factor for arterial thrombotic disease. Br J Haematol 1997;99:304-307.
Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. New Engl J Med 1995; 332:912-917.
Kohler HP, Stickland MH, Ossei-Gerning N, Carter A, Mikkola H, Grant PJ. Association of a common polymorphism in the factor XIII gene with myocardial infarction. Thromb Haemost 1998;79:8-13.
Marcheti G, Patracchini P, Papacchini M, Farrati M, Bernardi F. A poymorphism in the 5' region of the coagulation factor VII gene caused by an inserted decanucleotide. Hum Genet 1993;90:575-576.
Marchetti G, Patracchini P, Gemmati D, et al. Detection of two missense mutations and characterization of a repeat polymorphism in the factor VII gene (F7). Hum Genet 1992;89:497-502.
Humphries S, Templ A, Lane A, Green F, Cooper J, Miller G. Low plasma levels of factor VIIc and antigen are more strongly associated with the 10 bas pair promoter (-323) insertion than the glutamin 353 variant. Thromb Haemost 1996;75:567-573.
DellAcqua G, lacoviello L, D'Orazio A, Di Bitondo R, Castelnuovo A, Donati MB. A polymorphic cluster in the 5' region of the human coagulation factor VII gene: Detection frequency and linkage disequilibrium. Thromb Res 1997;88:445-448.
van't Hooft FM, Silveira A, Tornvall P, et al. Two common functional polymorphisms in the promoter region of the coagulation factor VII gene determining plasma factor VII activity and mass concentration. Blood 1999;93:3432-3441.
Lane A, Green F, Scarabin PY, et al. Factor VII Arg/Gln353 polymorphism determines factor VII coagulant activity in patients with myocardial infarction (MI) and control subjects in Belfast and in France but is not a strong indicator of MI risk in the ECTIM study. Atherosclerosis 1996;119:119-127.
Iacoviello L, Di Castelnuovo A, de Knijff P, Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction. N Engl J Med 1998;338:79-85.
Corral J, Gonzalez-Conjero R, Lozano ML, Rivera J, Vicente V. Genetic polymorphisms of factor VII are not associated with arterial thrombosis. Blood Coagul Fibrinolysis 1998;9:267-272.
Lane A, Cruickshank JK, Stewart J, Henderson A, Humphries S, Green F. Genetic and environmental deerminants of factor VII coagulant activity in different ethnic groups at differing risk of coronary heart disease. Atherosclerosis 1992;94:43-50.
de Maat MP, Green F, de Knijff P, Jespersen J, Kluft C. Factor VII polymorphisms in population with different risks of cardiovascular disease. Arterioscler Thromb Vasc Biol 1997;17:1918-1922.
Pollak ES, Hung HL, Godin W, Overton GC, High KA. Functional characterization of the human factor VII 5' flanking region. J Biol Chem 1996;271:1738-1747.
Sacchi E, Tagliabue A, Scoglio R, et al. Plasma factor VII levels are influenced by a polymorphism in the promoter region of the FVII gene. Blood Coagul Fibrinolysis 1996;7:114-117.
Bernardi F, Marchetti G, Pinotti M, et al. Factor VII gene polymorphisms contribute about one third of the factor VII level variation in plasma. Arterioscer Thromb Vasc Biol 1996;16:72-76.
Rosendaal FR, Doggen CJM, Zivelin A, et al. Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost 1998;79(4):706-708.
Cox MJ, Rees DC, Martinson JJ, Clegg JB. Evidence for a single origin of factor V Leiden. Br J Haematol 1996;92:1022-1025.
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Jimenez-Boj, E., Schüttrumpf, J., Forberg, E. et al. The Decanucleotide Polymorphism in the Factor VII Promoter Predicts Factor VII Plasma Levels but not the Risk of Acute Coronary Syndromes. J Thromb Thrombolysis 10, 23–28 (2000). https://doi.org/10.1023/A:1018790519492
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DOI: https://doi.org/10.1023/A:1018790519492