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DOI: 10.1055/s-0037-1614482
Genetic Effects for Plasma Factor VII Levels Independent of and in Common with Triglycerides
The SATSA (Swedish Adoption/Twin Study of Aging) has been supported by grants from the National Institute of Aging (AG-04563, AG-10175), the MacArthur Foundation Research Network on Successful Aging, and the Swedish Council for Social Research. In addition, support for this study has been provided by the Swedish Medical Research Council (09533), King Gustav the V and Queen Victoria’s Foundation, and the Swedish Lung and Heart Foundation.Publikationsverlauf
Received04. Juni 1998
Accepted after revision02. Dezember 1998
Publikationsdatum:
09. Dezember 2017 (online)
Summary
Background. Coagulation factor VII has been demonstrated as a potential risk factor for cardiovascular disease. Both genes and non-genetic factors are related to plasma levels of factor VII. However, the extent to which genetic effects influence variability in plasma factor VII levels is unknown. Further, increased levels of plasma factor VII are associated with serum triglycerides, yet the reason for this association is not fully understood. Methods and Results. Quantitative genetic analyses were applied to evaluate the relative importance of genetic and different environmental influences on plasma factor VII levels and to test the significance of genetic and environmental factors in common to factor VII and triglycerides in 215 pairs of middle-aged and elderly twins, of whom 104 were reared apart and 120 were women. Genetic influences were found to account for 57% of the individual differences in plasma factor VII levels, whereas shared-rearing and residual-familial environmental factors were not significant. Furthermore, a significant genetic correlation of 0.38 was found between factor VII and triglycerides, but the environmental correlation between these two measures was not significant. Genetic factors in common to factor VII and triglycerides explain about 7% of the total variance for factor VII. Conclusion. The present study suggests that there are substantial genetic influences on plasma factor VII levels. Furthermore, genetic effects explain the phenotypic association between factor VII and triglycerides.
* Current address: Dr. Y. Hong, Division of Biostatistics, Washington University School of Medicine, Campus Box 8067, 660 S. Euclid, St. Louis, MO 63110, USA
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References
- 1 Davie EW. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 1991; 30: 10363-70.
- 2 Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WRS, Haines AP, Stirling Y, Imeson JD, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; ii: 533-7.
- 3 Hoffman CJ, Miller RH, Lawson WE, Hultin MB. Elevation of factor VII activity and mass in young adults at risk of ischemic heart disease. J Am Coll Cardiol 1989; 14: 941-6.
- 4 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.
- 5 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: 54-9.
- 6 Cortellaro M, Baldassarre D, Cofrancesco E, Tremoli E, Colombo A, Boschetti C, Paoletti R. Relation between hemostatic variables and increase of common carotid intima-media thickness in patients with peripheral arterial disease. Stroke 1996; 27: 450-4.
- 7 Green D, Ruth KJ, Folsom AR, Liu K. Hemostatic factors in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Arterioscler Thromb 1994; 14: 686-93.
- 8 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.
- 9 de Grouchy J, Dautzenberg MD, Turleau C, Beguin S, Chavin-Colin F. Regional mapping of clotting factors VII and X to 13q34: expression of factor VII through chromosome 8. Hum Genet 1984; 66: 230-3.
- 10 Fagan K, Wilkinson I, Allen M, Brownlea S. The coagulation factor VII regulator is located on 8p23.1. Hum Genet 1988; 79: 365-7.
- 11 Green F, Kelleher C, Wilkes H, Temple A, Meade T. Humphries. A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals. Arterioscler Thromb 1991; 11: 540-6.
- 12 Green F, Humphries S. Genetic determinants of arterial thrombosis. Bail-lieres Clin Haematol 1994; 7: 675-92.
- 13 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: 617-22.
- 14 Sacchi E, Tagliabue L, Scoglio R, Baroncini C, Coppola R, Bernardi F, Manucci PM. Plasma factor VII levels are influenced by a polymorphism in the promoter region of the FVII gene. Blood Coagul Fibrinolysis 1996; 7: 114-7.
- 15 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.
- 16 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.
- 17 Miller GJ, Martin JC, Webster J, Wilkes H, Miller NE, Wilkinson WH, Meade TW. Association between dietary fat intake and plasma factor VII coagulant activity – a predictor of cardiovascular mortality. Atherosclerosis 1986; 60: 269-77.
- 18 Connelly JB, Cooper JA, Meade TW. Strenous exercise, plasma fibrinogen, and factor VII activity. Br Heart J 1992; 67: 351-4.
- 19 Barker DJP, Meade TW, Fall CHD, Lee A, Osmond C, Phipps K, Stirling Y. Relation of fetal and infant growth to plasma fibrinogen and factor VII concentrations in adult life. BMJ 1992; 304: 148-52.
- 20 Mitropoulos KA. Hypercoagulabilibity and factor VII in hypertriglyceridemia. Semin Thromb Hemost 1988; 80: 227-33.
- 21 Conlan MG, Folsom AR, Finch A, Davis CE, Sorlie P, Marcucci G, Wu KK. Association of factor VIII and von Willebrand factor with age, race, sex and risk factors for atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. Thromb Haemost 1993; 70: 380-5.
- 22 Negi M, Arigliano PL, Talamini G, Carlini S, Manzato F, Bonadonna G. Levels of plasma factor VII and factor VII activated forms as a function of plasma triglyceride levels. Atherosclerosis 1993; 99: 55-61.
- 23 Cushman M, Yanez D, Psaty BM, Fried LP, Heiss G, Lee M, Polak JF, Savage PJ, Tracy RP. Association of fibrinogen and coagulation factors VII and VIII with cardiovascular risk factors in the elderly – The Cardiovascular Health Study. Am J Epidemiol 1996; 143: 665-76.
- 24 Silveira A, Karpe F, Blombäck M, Steiner G, Walldius G, Hamsten A. Activation of coagulation factor VII during alimentary lipemia. Arterioscler Thromb 1994; 14: 60-9.
- 25 Miller GJ, Martin JC, Mitropoulos KA, Esnouf MP, Cooper JA, Morrissey JH, Howarth DJ, Tuddenham EGD. Activation of factor VII during alimentary lipidemia occurs in healthy adults and patients with congenital factor XII or factor XI deficiency, but not in patients with factor IX deficiency. Blood 1996; 87: 4187-96.
- 26 Sanders TA, Miller GJ, de Grass T, Yahia N. Postprandial activation of coagulant factor VII by long-chain dietary fatty acids. Thromb Haemost 1996; 76: 369-71.
- 27 Glueck CJ, Glueck I H, Tracy T, Speirs J, Stroop D. Inheritance conjointly contributing to fibrinolysis and hyperlipidemia. Metabolism 1993; 42: 1410-9.
- 28 Pedersen NL, Friberg L, FloderuS-Myrhed B, McClearn GE, Plomin R. Swedish early separated twins: identification and characterization. Acta Genet Med Gemellol (Roma) 1984; 33: 243-50.
- 29 Pedersen NL, McClearn GE, Plomin R, Nesselroade JR, Berg S, de Faire U. The Swedish Adoption Twin study of Aging: an update. Acta Gent Med Gemellol (Roma) 1991; 40: 7-20.
- 30 Avvisati G, ten Cate JW, van Wijk EM, Kahle LH, Mariani G. Evaluation of a new chromogenic assay for factor VII and its application in patients on oral anticoagulant treatment. Br J Haematol 1980; 45: 343-52.
- 31 McGue M, Bouchard Jr. TJ. Adjustment of twin data for the effects of age and sex. Behav Genet 1984; 14: 325-43.
- 32 SAS Procedures and SAS/STAT User’ Guide. Version 6. Fourth Edition. Gary, North Carolina: SAS Institute Inc; 1994
- 33 Falconer DS. Introduction to Quantitative Genetics. 3rd ed. Esgender, England: London Scientific and Technical; 1989
- 34 Jöreskog KG, örbom D. LISREL 7: A guide to the program and application. 2nd ed. Chicago, Ill: SPSS; 1989
- 35 Heller DA, Pedersen NL, de Faire U, McClearn GE. Genetic and environmental correlations among serum lipids and apolipoproteins in elderly twins reared together and apart. Am J Hum Genet 1994; 55: 1255-67.
- 36 Hong Y, Pedersen NL, Egberg N, de Faire U. Moderate genetic influences on plasma levels of plasminogen activator inhibitor-1 and evidence of genetic and environmental influences shared by plasminogen activator inhibitor-1, triglycerides, and body mass index. Arterioscler Thromb Vasc Biol 1997; 17: 2776-82.
- 37 Neale MC, Cardon LR. Methodology for Genetic Studies of Twins and Families. Dordrecht, the Netherlands: Kluwer Academic Publishers; 1992
- 38 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 1991; 94: 43-50.
- 39 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. Arterioscler Thromb 1994; 14: 1923-7.
- 40 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. Arterioscler Thromb 1994; 14: 193-8.
- 41 Cigolini M, Targher G, Agostino G, Tonoli M, Muggeo M, de Sandre G. Liver steatosis and its relation to plasma haemostatic factors in apparently healthy men – role of the metabolic syndrome. Thromb Haemost 1996; 76: 69-73.
- 42 Coleman T, Seip RL, Gimble JM, Lee D, Maeda N, Semenkovich CF. COOH-terminal disruption of lipoprotein lipase in mice is lethal in homo-zygotes, but heterozygotes have elevated triglycerides and impared enzyme activity. J Biol Chem 1995; 270: 12518-25.
- 43 Mitropoulos KA, Miller GJ, Watts GF, Durrington PN. Lipolysis of triglyceride-rich lipoproteins activates coagulant factor VII: a study in familial lipoprotein-lipase deficiency. Atherosclerosis 1992; 95: 119-25.
- 44 Dorner G, Plagemann A. Perinatal hyperinsulinism as possible predisposing factor for diabetes mellitus, obesity and enhanced cardiovascular risk in later life. Horm Metab Res 1994; 26: 213-21.