Download PDF
Thromb Haemost 1996; 75(03): 401-406
DOI: 10.1055/s-0038-1650286
Original Article
Schattauer GmbH Stuttgart

Factor VII Gene Polymorphisms, Factor VII:C Levels and Features of Insulin Resistance in Non-Insulin-Dependent Diabetes mellitus

Daniella M Heywood
The Diabetes and Thrombosis Research Group, Division of Medicine, School of Medicine, University of Leeds, UK
,
Michael W Mansfield
The Diabetes and Thrombosis Research Group, Division of Medicine, School of Medicine, University of Leeds, UK
,
Peter J Grant
The Diabetes and Thrombosis Research Group, Division of Medicine, School of Medicine, University of Leeds, UK
› Author Affiliations
Further Information

Publication History

Received: 22 August 1995

Accepted after resubmission10 November 1995

Publication Date:
26 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

The macrovascular complications of non-insulin-dependent diabetes mellitus (NIDDM) are related to the features of insulin resistance (IR). High Factor VII :C (FVII:C) levels are associated with increased cardiovascular risk and relate to a base change in the FVII gene detected by Msp I endonuclease, and also to an insertion polymorphism in the promoter region. To examine the association between FVII:C levels, genotype and features of IR, 95 NIDDM patients were studied. Genotype was related to FVII:C levels (M1M1 137%, n = 75; M1M2 and M2M2 114%, n = 20, p <0.005; AA 136%, n = 71; Aa 119%, n = 21, p <0.05), which is consistent with previous studies in healthy populations. FVII: C correlated with cholesterol (r = 0.51, p <0.0005), insulin (r = 0.36, p = 0.002), triglycerides (r = 0.34, p = 0.001), age (r = 0.23, p <0.005) and body mass index (r = 0.23, p <0.05). When analysed by Msp I genotype, the stronger predictor of FVII: C levels, these correlations remained, with no difference in regression slopes. In a multiple regression model, genotype, cholesterol, insulin, and gender remained as independent predictors of FVII:C levels. In conclusion, FVII :C concentrations are elevated in NIDDM in relation to both FVII genotypes and features of IR.

 

  • References

  • 1 Kannel WB. Lipids, diabetes, and coronary heart disease: Insights from the Framingham study. Am Heart J 1985; 110: 1100-1106
    CrossrefPubMedSearch in Google Scholar
  • 2 Ganda OP. Pathogenesis of macrovascular disease in the human diabetic. Diabetes 1980; 29: 931-940
    CrossrefPubMedSearch in Google Scholar
  • 3 Pyorala K. Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease. Results from two population studies in Finland. Diabetes Care 1979; 2: 131-141
    CrossrefPubMedSearch in Google Scholar
  • 4 Broze Jr GJ, Majerus PW. Purification and properties of human coagulation factor VII. J Biol Chem 1980; 255: 1242-1247
    PubMedSearch in Google Scholar
  • 5 Nakagaki T, Foster DC, Berkner KL, Kisiel W. Initiation of the extrinsic pathway of blood coagulation: evidence for the tissue factor dependent autoactivation of human coagulation factor VII. Biochemistry 1991; 30: 10819-10824
    CrossrefPubMedSearch in Google Scholar
  • 6 Rao LMR, Rapaport SI. Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of blood coagulation. Proc Natl Acad Sci USA 1988; 85: 6687-6691
    CrossrefPubMedSearch in Google Scholar
  • 7 Meade TW, Mellows S, Brovic 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; 2: 533-537
    PubMedSearch in Google Scholar
  • 8 Balleisen L, Schulte H, Assman G, Epping PH, van de Loo J. Coagulation factors and the progress of coronary heart disease. Lancet 1987; 2: 461
    PubMedSearch in Google Scholar
  • 9 Meade TW, North WRS, Chakrabarti RR, Stirling Y, Haines AP, Thompson SG. Haemostatic function and cardiovascular death: Early results of a prospective study. Lancet 1980; 1: 1050-1054
    PubMedSearch in Google Scholar
  • 10 Meade TW, Imeson J, Stirling Y. Effects of changes in smoking and other characteristics on clotting factors and the risk of ischaemic heart disease. Lancet 1987; 2: 986-988
    PubMedSearch in Google Scholar
  • 11 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
    CrossrefPubMedSearch in Google Scholar
  • 12 Heinrich J, Balleisen L, Schulte H, Assman 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
    CrossrefPubMedSearch in Google Scholar
  • 13 Cortellaro M, Boschetti C, Cofrancesco E, Zaussi C, Catalano M, de Gaetano G, Gabrielli L, Lombardi B, Specchia G, Travazzi L, Tremoli E, della Volpe A, Polli E. the PLAT study group. The PLAT study: haemostatic function in relation to atherothrombotic ischaemic events in vascular disease patients: principal results. Arterioscler Thromb 1992; 12: 1063-1070
    CrossrefPubMedSearch in Google Scholar
  • 14 Green F, Kellener C, Wilkes H, Temple A, Meade T, Humphries S. A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals. Arterioscler Thromb 1991; 11: 540-546
    CrossrefPubMedSearch in Google Scholar
  • 15 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 diseases. Atherosclerosis 1992; 94: 4-50
    PubMedSearch in Google Scholar
  • 16 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: 193-198
    CrossrefPubMedSearch in Google Scholar
  • 17 Saha N, Liu Y, Heng CK, Hong S, Low PS, Tay JSH. Association with factor VII genotype with plasma factor VII activity and antigen levels in healthy Indian adults and interaction with triglycerides. Arterioscler Thromb 1994; 14: 1923-1927
    CrossrefPubMedSearch in Google Scholar
  • 18 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: 623-625
    Thieme ConnectPubMedSearch in Google Scholar
  • 19 Kario K, Narita N, Matsuo T, Kay aba K, Tsutsumi A, Matsuo M, Miyata T, Shimada K. Genetic determinants of plasma factor VII activity in the Japanese. Thromb Haemost 1995; 73: 617-622
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Arbini AA, Bauer KA. Reduced plasma factor VII coagulant activity due to the Arg353Gln polymorphism in the factor VII gene results from defective secretion (Abstract). Blood 1994; 86 (Suppl. 01) Suppl 86
    PubMedSearch in Google Scholar
  • 21 Miller GJ, Walter SJ, Stirling Y, Thompson SG, Esnouf MP, Meade TW. Assay of factor VII activity by two techniques: evidence of increased conversion of VII to aVII in hyperlipidaemia, with possible implications for ischaemic heart disease. Br J Haematol 1985; 59: 249
    CrossrefPubMedSearch in Google Scholar
  • 22 Simpson HCR, Meade TW, Stirling Y, Mann JI, Chakrabarti R, Woolf L. Hypertriglyceridaemia and hypercoagulability. Lancet 1983; i: 786-790
    PubMedSearch in Google Scholar
  • 23 Miller GJ, Martin JC, Mitropoulos KA, Reeves BEA, Thompson RL, Meade TW, Cooper JA, Cruickshank JK. Plasma FVII is activated by postprandial triglyceridaemia irrespective of dietary fat composition. Atherosclerosis 1991; 86: 163-171
    CrossrefPubMedSearch in Google Scholar
  • 24 Van der Bom JG, Bots ML, Van Vilet HHDM, Hofman A, Grobbee DE. Factor VII coagulant activity is related to blood lipids in the elderly. The Rotterdam study. Fibrinolysis 1994; 8: 132-114
    PubMedSearch in Google Scholar
  • 25 Marchetti G, Patracchini P, Papacchini M, Ferrati M, Bemardi F. A polymorphism in the 5’ region of coagulation factor VII gene (F7) caused by an inserted decanucleotide. Hum Genet 1993; 90: 575-576
    PubMedSearch in Google Scholar
  • 26 Mariani G, Marchetti G, Arcieri P, Bemardi F. The role of factor VII gene polymorphisms in determining FVII activity and antigen plasma level variation (abstract). Blood 1994; 86 (Suppl. 01) Suppl 86
    PubMedSearch in Google Scholar
  • 27 Mansfield MW, Stickland MH, Grant PJ. Environmental and genetic factors in relation to elevated circulating levels of Plasminogen activator inhibitor-1 in Caucasian patients with Non-Insulin-Dependent Diabetes Mellitus. Thromb Haemost 1995; 74: 842-847
    Thieme ConnectPubMedSearch in Google Scholar
  • 28 Mansfield MW, Stickland MH, Carter A, Grant PJ. Polymorphisms of the plasminogen activator inhibitor-1 gene in type 1 and type 2 diabetes and in patients with diabetic retinopathy. Thromb Haemost 1994; 71: 731-736
    Thieme ConnectPubMedSearch in Google Scholar
  • 29 Armitage P, Berry G. Statistical methods in medical research. 2nd edition. Oxford: Blackwell 1987: 273-295
    PubMedSearch in Google Scholar
  • 30 The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.. N Engl J Med 1993 329. 977-986
    PubMedSearch in Google Scholar
  • 31 Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607
    CrossrefPubMedSearch in Google Scholar
  • 32 Landin K, Stigendal L, Eriksson E, Krotkiewski M, Risberg B, Tengbom L, Smith U. Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1. Metabolism 1990; 39: 1044-1048
    CrossrefPubMedSearch in Google Scholar
  • 33 Landin K, Tengbom L, Smith U. Elevated fibrinogen and plasminogen activator inhibitors (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular disease. J Int Med 1990; 227: 273-278
    CrossrefPubMedSearch in Google Scholar
  • 34 Ernst E, Ludwig Resch K. Fibrinogen as a cardiovascular risk factor: A meta analysis review of the literature. Ann Int Med 1993; 118: 956-963
    CrossrefPubMedSearch in Google Scholar
  • 35 Balleisen L, Bailey J, Epping PH, Schulte H, Van de Loo J. Epidemiological study on Factor VII, Factor VIII and fibrinogen in an industrial population: 1. Baseline data on the relation to age, gender, body weight, smoking, alcohol, pill using and menopause. Thromb Haemost 1985; 54 (02) 475-479
    Thieme ConnectPubMedSearch in Google Scholar
  • 36 Miller GJ, Stirling Y, Esnouf MP, Heinrich J, van de Loo J, Keinast J, Wu KK, Morrissey JH, Meade TW, Martin JC, Imeson JK, 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: 38-48
    Thieme ConnectPubMedSearch in Google Scholar