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Thromb Haemost 1994; 72(05): 734-739
DOI: 10.1055/s-0038-1648950
Original Article
Schattauer GmbH Stuttgart

Elevated Levels of Factor VII Activity in the Postprandial State: Effect of the Factor VII Arg-GIn Polymorphism

Angela Silveira
1   The Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Stockholm, Sweden
,
Fiona Green
3   Centre for Genetics of Cardiovascular Disorders, Department of Medicine, University College London Medical School, London, UK
,
Fredrik Karpe
1   The Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Stockholm, Sweden
,
Margareta Blombäck
2   Depatment of Clinical Chemistry and Blood Coagulation, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden
,
Steve Humphries
3   Centre for Genetics of Cardiovascular Disorders, Department of Medicine, University College London Medical School, London, UK
,
Anders Hamsten
1   The Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Stockholm, Sweden
› Author Affiliations
Further Information

Publication History

Received 26 May 1994

Accepted 12 July 1994

Publication Date:
06 July 2018 (online)

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Summary

A genetic polymorphism (Arg/Gln353) of coagulation factor VII was recently identified and shown to be associated with differences in basal factor VII coagulant activity. Postprandial lipaemia seems to exert an acute but evanescent effect on the activity of factor VII, and the influence of the Arg/Gln353 polymorphism on factor VII activation during postprandial lipaemia was therefore studied in male post-infarction patients [age 48.8 ± 3.3 years (mean ± SD)] with Arg/Arg (n = 23) and Arg/Gln (n = 8) genotypes. Factor VII antigen (VIlag) and activity along with plasma lipoproteins were determined before and after intake of a mixed meal-type of oral fat load. Patients with the Arg/Gln genotype had basal VIlag and activated factor VII (Vila) levels 75% and 48%, respectively, of those of patients homozygous for the Arg allele. In absolute terms, Vila increased more in homozygotes for the Arg allele (AO-6 h Vila 1.76 ± 1.48 ng/ml) than in heterozygotes (0.60 ± 0.27 ng/ml) in response to fat intake, but the percentage increase in Vila molecules did not differ significantly between subjects with Arg/Arg and Arg/Gln genotypes (37 ± 32% versus 27 ± 15%). This suggests that the influence of the Arg/Gln polymorphism on factor VII activity is mainly accounted for by differences in the basal factor VII protein level between genotypes. Since most of our lives are spent in the postprandial state, possession of the factor VII-Gln353 allele is likely to confer protection against coronary heart disease by reducing the amount of Vila produced in response to fat intake.

 

  • References

  • 1 Meade TW, North WRS, Chakrabarti R, Stirling Y, Haines AP, Thompson SG. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet 1980; i: 1050-1054
    PubMedSearch in Google Scholar
  • 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: 533-537
    PubMedSearch in Google Scholar
  • 3 Miller GJ, Cruickshank JK, Ellis LJ, Thompson RL, Wilkes HC, Stirling Y, Mitropoulos KA, Allison JV, Fox TE, Walker AO. Fat consumption and factor VII coagulant activity in middle-aged men. An association between a dietary and thrombogenic coronary risk factor. Atherosclerosis 1989; 78: 19-24
    CrossrefPubMedSearch in Google Scholar
  • 4 Mitropoulos KA, Esnouf MP, Meade TW. Increased factor VII coagulant activity in the rabbit following diet-induced hypercholesterolaemia. Evidence for increased conversion of VII to αVIIa and higher flux within the cogulation pathway. Atherosclerosis 1987; 63: 43-52
    CrossrefPubMedSearch in Google Scholar
  • 5 Mitropoulos KA, Miller GJ, Reeves BEA, Wilkes HC, Cruickshank JK. Factor VII coagulant activity is strongly associated with the plasma concentration of large lipoprotein particles in middle-aged men. Atherosclerosis 1989; 76: 203-208
    CrossrefPubMedSearch in Google Scholar
  • 6 Miller GJ, Martin JC, Mitropoulos KA, Reeves BEA, Thompson RL, Meade TW, Cooper JA, Cruickshank JK. Plasma factor VII is activated by postprandial triglyceridaemia, irrespective of dietary fat composition. Atherosclerosis 1991; 86: 163-171
    CrossrefPubMedSearch in Google Scholar
  • 7 Mitropoulos KA, Miller GJ, Watts GF, Durrington PN. Lipolysis of triglyceride-rich lipoproteins activates coagulant factor XII: a study in familial lipo-protein-lipase deficiency. Atherosclerosis 1992; 95: 119-125
    CrossrefPubMedSearch in Google Scholar
  • 8 Miller GJ, Walter SJ, Stirling Y, Thompson SG, Esnouf MP, Meade TW. Assay of factor VII activity by two techniques: evidence for increased conversion of VII to αVIIa in hyperlipidaemia, with possible implications for ischaemic heart disease. Br J Haematol 1985; 59: 249-258
    CrossrefPubMedSearch in Google Scholar
  • 9 Carvalho de Sousa J, Bruckert E, Giral P, Soria C, Chapman J, Truffert J, Dairou F, de Gennes JL, Caen JP. Coagulation factor VII and plasma triglycerides. Decreased catabolism as a possible mechanism of factor VII hyperactivity. Haemostasis 1989; 19: 125-130
    PubMedSearch in Google Scholar
  • 10 Hoffman CJ, Miller RH, Hultin MB. Correlation of factor VII activity and antigen with cholesterol and triglycerides in healthy young adults. Arterioscler Thromb 1992; 12: 267-270
    CrossrefPubMedSearch in Google Scholar
  • 11 Silveira A, Karpe F, Blomback M, Walldius G, Steiner G, Hamsten A. Activation of coagulation factor VII during alimentary lipemia. Arterioscler Thromb 1994; 14: 60-69
    CrossrefPubMedSearch in Google Scholar
  • 12 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. Arterioscler Thromb 1991; 11: 540-546
    CrossrefPubMedSearch in Google Scholar
  • 13 Lane A, Cruickshank JK, Mitchell J, Henderson A, Humphries S, Green F. Genetic and environmental determinants of factor VII coagulant activity in different ethnic groups at differing risk of coronary heart disease. Atherosclerosis 1992; 94: 43-50
    CrossrefPubMedSearch in Google Scholar
  • 14 Humphries SE, Lane A, Green F, Cooper J, Miller G. Factor VII coagulant activity and antigen levels in men are determined by interaction between factor VII genotype and plasma triglyceride concentration. Arterioscler Thromb 1994; 14: 193-198
    CrossrefPubMedSearch in Google Scholar
  • 15 Karpe F, Steiner G, Olivecrona T, Carlson LA, Hamsten A. Metabolism of triglyceride-rich lipoproteins during alimentary lipemia. J Clin Invest 1993; 91: 748-758
    CrossrefPubMedSearch in Google Scholar
  • 16 Hamsten A, Blomback M, Wiman B, Svensson J, Szamosi A, de Faire U, Mettinger L. Haemostatic function in myocardial infarction. Br Heart J 1986; 55: 58-66
    CrossrefPubMedSearch in Google Scholar
  • 17 van Deijk WA, van Dam-Mieras MCE, Muller AD, Hemker HC. Evaluation of a coagulation assay determining the activity state factor VII in plasma. Haemostasis 1983; 13: 192-197
    PubMedSearch in Google Scholar
  • 18 Owren PA, Aas K. The control of dicumarol therapy and the quantitative determination of prothrombin and proconvertin. Scand J Clin Lab Invest 1951; 3: 201-218
    CrossrefPubMedSearch in Google Scholar
  • 19 Wildgoose P, Nemerson Y, Hansen LL, Nielsen FE, Glazer S, Hedner U. Measurement of basal levels of factor Vila in Hemophilia A and B patients. Blood 1992; 80: 25-28
    PubMedSearch in Google Scholar
  • 20 Morrisey JH, Macik BG, Neuenschwander PF, Comp PC. Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation. Blood 1993; 81: 734-744
    PubMedSearch in Google Scholar
  • 21 Fiore M, Neuenschwander PF, Morrisey JH. The biochemical basis for the apparent defect of soluble mutant tissue factor in enhancing the proteolytic activities of factor Vila. J Biol Chem 1994; 269: 143-9
    PubMedSearch in Google Scholar
  • 22 Talmud PJ, Bami N, Kessling A, Carlsson P, Damfors C, Bjursell G, Galton D, Wynn V, Kirk H, Hayden M, Humphries S. Apolipoprotein B gene variants are involved in the determination of serum cholesterol levels: A study in normo- and hyperlipidaemic individuals. Atherosclerosis 1987; 67: 81-89
    CrossrefPubMedSearch in Google Scholar
  • 23 Poapst M, Uffelman K, Steiner G. The chromogenicity and quantitation of apo B-100 and apo B-48 of human plasma lipoproteins on analytical SDS gel electrophoresis. Atherosclerosis 1987; 65: 75-88
    CrossrefPubMedSearch in Google Scholar
  • 24 Reardon MF, Poapst ME, Uffelmany KD, Steiner G. Improved method for quantitation of B apoprotein in plasma lipoproteins by electroimmunoassay. Clin Chem 1981; 27: 892-895
    PubMedSearch in Google Scholar
  • 25 Carlson K. Lipoprotein fractionation. J Clin Pathol 1973; 5 (Suppl. 26) 32-37
    PubMedSearch in Google Scholar
  • 26 Zlatkis A, Zak B, Boyle A. A new method for direct determination of serum cholesterol. J Lab Clin Med 1953; 41: 486-492
    PubMedSearch in Google Scholar
  • 27 Fletcher MJ. A colorimetric method for estimating serum triglycerides. Clin Chim Acta 1968; 22: 393-397
    CrossrefPubMedSearch in Google Scholar
  • 28 Carlson LA. Determination of serum triglycerides. J Atheroscler Res 1963; 3: 334-336
    CrossrefPubMedSearch in Google Scholar
  • 29 Bengtsson-Olivecrona G, Olivecrona T. Assay of lipoprotein lipase and hepatic lipase. In: Lipoprotein analysis. A practical approach Skinner RE, Converse CA. eds Oxford University Press; Oxford, England: 1992: 169-174
  • 30 Mitropoulos KA, Reeves BEA, O’Brien DP, Cooper JA, Martin JC. The relationship between factor VII coagulant activity and factor XII activation induced in plasma by endogenous or exogenously added contact surface. Blood Coag Fibrinol 1993; 4: 223-234
    CrossrefPubMedSearch in Google Scholar
  • 31 Mitropoulos KA, Reeves BEA, Miller GJ. The activation of factor VII in citrated plasma by charged long-chain saturated fatty acids at the interface of large triglyceride-rich lipoproteins. Blood Coag Fibrinol 1993; 4: 943-951
    CrossrefPubMedSearch in Google Scholar
  • 32 Mitropoulos KA, Miller GJ, Martin JC, Reeves BEA, Cooper J. Dietary fat induces changes in factor VII coagulant activity through effects on plasma free stearic acid concentration. Arterioscler Thromb 1994; 14: 214-222
    CrossrefPubMedSearch in Google Scholar