A Genetic Propensity to High Factor VII Is not Associated with the Risk of Myocardial Infarction in Men
16 July 1997
Accepted after resubmission 16 April 1998
08 December 2017 (online)
Several studies have examined the relation between factor VII and coronary artery disease by measuring factor VII levels in plasma and some found an association between high levels and disease. This suffers problems of interpretation concerning the causality of high factor VII levels, because factor VII levels may be affected by atherogenic risk factors and may become elevated as a consequence of atherosclerosis. We investigated the association between a genetic variant (353Arg→Gln), shown to be related to factor VII levels, and myocardial infarction in a large case-control study, including 560 cases and 644 controls. Individuals carrying the 353Arg-Arg genotype seemed to have a lower risk of myocardial infarction (odds ratio 0.80 [95% confidence interval 0.60-1.06]). In this study, we confirmed higher factor VII antigen and activity level in 529 men homozygous for the 353Arg allele compared with 115 men carriers of the 353Gln allele (around 20% higher).
Our results indicate that a genetic propensity to high factor VII levels is not associated with the risk of myocardial infarction. Since we confirmed the association of the 353Arg-Arg genotype with higher factor VII levels, we conclude that high levels of factor VII are not a causal determinant of myocardial infarction.
* Present address: Dr. P. H. Reitsma, Laboratory for Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
- 1 Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342: 1076-9.
- 2 Junker R, Heinrich J, Schulte H, van de Loo J, Assmann G. Coagulation factor VII and the risk of coronary heart disease in healthy men. Arterioscler Thromb Vasc Biol 1997; 17: 1539-44.
- 3 Smith FB, Lee AJ, Fowkes FGR, Price JF, Rumley A, Lowe GDO. Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study. Arterioscler Thromb Vasc Biol 1997; 17: 3321-5.
- 4 Broadhurst P, Kelleher C, Hughes L, Imeson JD, Raftery EB. Fibrinogen, factor VII clotting activity and coronary artery disease severity. Atherosclerosis 1990; 85: 169-73.
- 5 Ho C, Wang S, Jap T. Hemostatic risk factors of coronary artery disease in the Chinese. Int J Cardiol 1995; 51: 79-84.
- 6 Carvalho De Sousa J, Azevedo J, Soria C, Barros F, Ribeiro C, Parreira F, Caen JP. Factor VII hyperactivity in acute myocardial thrombosis. A relation to the coagulation activation. Thromb Res 1988; 51: 165-73.
- 7 Suzuki T, Yamauchi K, Matsushita T, Furumichi T, Furui H, Tsuzuki J, Saito H. Elevation of factor VII activity and mass in coronary artery disease of varying severity. Clin Cardiol 1991; 14: 731-6.
- 8 Vaziri ND, Kennedy SC, Kennedy D, Gonzales E. Coagulation, fibrinolytic, and inhibitory proteins in acute myocardial infarction and angina pectoris. Am J Med 1992; 93: 651-7.
- 9 Sandset PM, Sirnes PA, Abildgaard U. Factor VII and extrinsic pathway inhibitor in acute coronary disease. Brit J Haematol 1989; 72: 391-6.
- 10 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 (02) 161-5.
- 11 Miller GJ, Stirling Y, Esnouf MP, Heinrich J, van de Loo J, Kienast J, Wu KK, Morrissey JH, Meade TW, Martin JC, Imeson JD, Cooper JA, Finch A. Factor VII deficient substrate plasmas depleted of protein C raise the sensitivity of the factor VII bio-assay to activated factor VII: an international study. Thromb Haemost 1994; 71 (01) 38-48.
- 12 Balleisen L, Bailey J, Epping P-H, Schulte H, van de Loo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population: I. Baseline data on the relation to age, gender, body-weight, smoking, alcohol, pill-using, and menopause. Thromb Haemost 1985; 54 (02) 475-9.
- 13 Balleisen L, Assmann G, Bailey J, Epping P-H, Schulte H, van de Loo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population - II. Baseline data on the relation to blood pressure, blood glucose, uric acid, and lipid fractions. Thromb Haemost 1985; 54 (03) 721-3.
- 14 Scarabin P, Vissac A, Kirzin J, Bourgeat P, Amiral J, Agher R, Guize L. Population correlates of coagulation factor VII. Importance of age, sex, and menopausal status as determinants of activated factor VII. Arterioscler Thromb Vasc Biol 1996; 16: 1170-6.
- 15 Stary HC. Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. Arterioscl Suppl 1989; 9: I-19-32.
- 16 Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscl Thromb 1991; 11: 1245-9.
- 17 Green F, Kelleher C, Wilkes H, Temple A, Meade T, Humphries S. A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals. Arterioscl Thromb 1991; 11: 540-6.
- 18 Lane A, Cruickshank JK, Mitchell J, Henderson A, Humphries S, Green F. Genetic and environmental determinants of factor VII coagulant activity in ethnic groups at differing risk of coronary heart disease. Atherosclerosis 1992; 94: 43-50.
- 19 Humphries SE, Green FR, Temple A, Dawson S, Henney A, Kelleher CH, Wilkes H, Meade TW, Wiman B, Hamsten A. Genetic factors determining thrombosis and fibrinolysis. Ann Epidemiol 1992; 2: 371-85.
- 20 Saha N, Liu Y, Heng CK, Hong S, Low PS, Tay JSH. Association of factor VII genotype with plasma factor VII activity and antigen levels in healthy Indian adults and interaction with triglycerides. Arterioscl Thromb 1994; 14: 1923-7.
- 21 Humphries SE, Lane A, Green FR, Cooper J, Miller GJ. Factor VII coagulant activity and antigen levels in healthy men are determined by interaction between factor VII genotype and plasma triglyceride concentration. Arterioscl Thromb 1994; 14: 193-8.
- 22 Bernardi F, Marchetti G, Pinotti M, Arcieri P, Baroncini c, Papacchini M, Zepponi E, Ursicino N, Chiarotti F, Mariani G. Factor VII gene polymorphisms contribute about one third of the factor VII level variation in plasma. Arterioscler Thromb Vasc Biol 1996; 16: 72-6.
- 23 Humphries S, Temple A, Lane A, Green F, Cooper J, Miller G. Low plasma levels of factor VIIc and antigen are more strongly associated with the 10 base pair promoter (-323) insertion than the glutamine 353 variant. Thromb Haemost 1996; 75 (04) 567-72.
- 24 Meilahn E, Ferrell R, Kiss J, Temple A, Green F, Humphries S, Kuller L. Genetic determination of coagulation factor VIIc levels among healthy middle-aged women. Thromb Haemost 1995; 73 (04) 623-5.
- 25 Lane A, Green F, Scarabin PY, Nicaud V, Bara L, Humphries S, Evans A, Luc G, Cambou JP, Arveiler D, Cambien F. 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: 119-27.
- 26 Bentzen J, Bladbjerg EM, de Maat MPM, Marckmann P. Plasma factor VII levels are determined by polymorphisms in the factor VII gene. Fibrinolysis 1996; 10 (Suppl. 02) 17-8.
- 27 Heywood DM, Mansfield MW, Grant PJ. Factor VII gene polymorphisms, factor VII:C levels and features of insulin resistance in non-insulin-dependent diabetes mellitus. Thromb Haemost 1996; 75 (03) 401-6.
- 28 Bernardi F, Arcieri P, Bertina RM, Chiarotti F, Corral J, Pinotti M, Prydz H, Samama M, Sandset PM, Strom R, Vicente Garcia V, Mariani G. Contribution of factor VII genotype to activated FVII levels. Differences in genotype frequencies between Northern and Southern European Populations. Arterioscler Thromb Vasc Biol 1997; 17: 2548-53.
- 29 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16 (03) 1215.
- 30 Bom VJJ, van Tilburg NH, Krommenhoek-van Es C, Bertina RM. Immunoradiometric assays for human coagulation factor VII using polyclonal antibodies against the Ca(II)-dependent and Ca(II)-independent conformation. Thromb Haemost 1986; 56 (03) 343-8.
- 31 Bertina RM, Orlando M, Tiedemann-Alderkamp GHJ. Preparation of a human factor VII deficient plasma. Thromb Res 1978; 13: 537-41.
- 32 Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet 1955; 19: 251-3.
- 33 Kario K, Narita N, Matsuo T, Kayaba K, Tsutsumi A, Matsuo M, Miyata T, Shimada K. Genetic determinants of plasma factor VII activity in the Japanese. Thromb Haemost 1995; 73 (04) 617-22.
- 34 Marchetti G, Patracchini P, Papacchini M, Ferrati M, Bernardi F. A polymorphism in the 5’ region of coagulation factor VII gene (F7) caused by an inserted decanucleotide. Hum Genet 1993; 90: 575-6.
- 35 Pollak ES, Hung H, Godin W, Overton GC, High KA. Functional characterization of the human factor VII 5’-flanking region. J Biol Chem 1996; 271 (03) 1738-47.
- 36 Hunault M, Arbini AA, Lopaciuk S, Carew JA, Bauer KA. The Arg353Gln polymorphism reduces the level of coagulation factor VII. In vivo and in vitro studies. Arterioscler Thromb Vasc Biol 1997; 17: 2825-9.
- 37 Arbini AA, Bauer KA. Reduced plasma factor VII coagulant activity due to the Arg353Gln polymorphism in the factor VII gene results from defective secretion. Blood 1994; 84: 86A.
- 38 Green F, Humphries S. Genetic determinants of arterial thrombosis. Baillière Clin Haem 1994; 7 (03) 675-92.
- 39 Lee KL, Woodlief LH, Topol EJ, Weaver WD, Betriu A, Col J, Simoons M, Aylward P, van de Werf F, Califf RM. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results from an international trial of 41 021 patients. Circulation 1995; 91: 1659-68.
- 40 Moor E, Silveira A, van’t Hooft F, Suontaka AM, Eriksson P, Blombäck M, Hamsten A. Coagulation factor VII mass and activity in young men with myocardial infarction at a young age. Role of plasma lipoproteins and factor VII genotype. Arterioscler Thromb Vasc Biol 1995; 15: 655-64.
- 41 Iacoviello L, Di Castelnuovo A, de Knijff P, D’Orazio A, Amore C, Arboretti R, Kluft C, Donati MB. Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction. N Engl J Med 1998; 338 (02) 79-85.