PDF herunterladen
Thromb Haemost 1998; 80(04): 592-597
DOI: 10.1055/s-0037-1615427
Rapid Communication
Schattauer GmbH

Genetic Modulation of Coagulation Factor VII Plasma Levels: Contribution of Different Polymorphisms and Gender-related Effects

Augusto Di Castelnuovo
1   From the Istituto di Ricerche Farmacologiche Mario Negri, Unit of Genetics of Vascular Risk Factors, “Angela Valenti” Laboratory of Thrombosis Pharmacology, Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Andria D’Orazio
1   From the Istituto di Ricerche Farmacologiche Mario Negri, Unit of Genetics of Vascular Risk Factors, “Angela Valenti” Laboratory of Thrombosis Pharmacology, Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Concetta Amore
1   From the Istituto di Ricerche Farmacologiche Mario Negri, Unit of Genetics of Vascular Risk Factors, “Angela Valenti” Laboratory of Thrombosis Pharmacology, Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Anna Falanga
2   From the Hematology Department of Ospedali Riuniti di Bergamo, Bergamo, Italy
,
Cornelis Kluft
3   From the Gaubius Laboratory, Leiden, The Netherlands
,
Maria Benedetta Donati
1   From the Istituto di Ricerche Farmacologiche Mario Negri, Unit of Genetics of Vascular Risk Factors, “Angela Valenti” Laboratory of Thrombosis Pharmacology, Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Licia Iacoviello
1   From the Istituto di Ricerche Farmacologiche Mario Negri, Unit of Genetics of Vascular Risk Factors, “Angela Valenti” Laboratory of Thrombosis Pharmacology, Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
3   From the Gaubius Laboratory, Leiden, The Netherlands
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 22. Januar 1998

Accepted after revision 13. Mai 1998

Publikationsdatum:
08. Dezember 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Summary

We studied the relationships among different polymorphisms of FVII gene in determining FVII levels, in a sample of 335 male and female Italian volunteers. The hypervariable region 4 (HVR4), the promoter decanucleotide insertion (-323 0/10 bp) and the R353Q polymorphisms of FVII gene were evaluated.

The association of HVR4 or -323 0/10 bp polymorphism with plasma FVII levels differed between gender (Interaction term: p = 0.02 and p = 0.03, respectively), showing stronger effect in males than in females. In males, the R353Q and the HVR4 polymorphisms showed an incremental influence on FVII variance (F = 8.9, p < 0.001 and F = 4.4, p = 0.01, respectively). Moreover, the effects of Q and 10 bp alleles on the reduction of FVII activity levels were significantly potentiated by the presence of H7 allele of HVR4 (Interaction term p = 0.03 for R353Q*HVR4 and p = 0.03 for -323 0/10 bp*HVR4). In conclusion, the effect of FVII polymorphisms on FVII levels was gender dependent and derived from a complex interaction among them. The HVR4 polymorphism seems to add an independent, albeit small, contribution to the regulation of FVII plasma levels.

 

  • References

  • 1 Meade TW, Brozovic M, Chakrabarti RR, Haines AP, Imeson JD, Mellow S, Miller GJ, North WRS, Stirling Y, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 2: 533-7.
    PubMedSuche in Google Scholar
  • 2 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.
    CrossrefPubMedSuche in Google Scholar
  • 3 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.
    CrossrefPubMedSuche in Google Scholar
  • 4 Balleisen L, Bailey J, Epping P-H, Schulte H, van de Loo J. Epidemio-logical 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: 475-9.
    Thieme ConnectPubMedSuche in Google Scholar
  • 5 Miller GJ, Martin JC, Mitropoulos KA. et al. Plasma factor VII is activated by postprandial triglyceridemia, irrespective of dietary fat composition. Atheroslerosis 1991; 86: 163-71.
    CrossrefPubMedSuche in Google Scholar
  • 6 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: 267-70.
    CrossrefPubMedSuche in Google Scholar
  • 7 Mennen LJ, Schouten EG, Grobbee DE, Kluft C. Coagulation factor VII, dietary fat and blood lipids: a review. Thromb Haemost 1996; 76: 492-9.
    Thieme ConnectPubMedSuche in Google Scholar
  • 8 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: 540-6.
    CrossrefPubMedSuche in Google Scholar
  • 9 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.
    CrossrefPubMedSuche in Google Scholar
  • 10 Silveira A, Green F, Karpe F, Blomback M, Humphries S, Hamsten A. Elevated levels of factor VII activity in the postprandial state: effect of the factor VII Arg-Gln polymorphism. Thromb Haemost 1994; 72: 734-9.
    Thieme ConnectPubMedSuche in Google Scholar
  • 11 O’Hara PJ, Grant FJ, Haldeman BA, Gray CL, Insley MY, Hagen FS, Murray MJ. Nucleotide sequence of the gene coding for human factor VII, a vitamin K-dependent protein participating in blood coagulation. Proc Natl Acad Sci USA 1987; 84: 5158-62.
    CrossrefPubMedSuche in Google Scholar
  • 12 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.
    CrossrefPubMedSuche in Google Scholar
  • 13 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.
    PubMedSuche in Google Scholar
  • 14 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 glutamine 353 variant. Thromb Haemost 1996; 75: 567-72.
    Thieme ConnectPubMedSuche in Google Scholar
  • 15 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: 79-85.
    CrossrefPubMedSuche in Google Scholar
  • 16 Maniatis T, Fritsch EF, Sambrook J. Molecular cloning: A laboratory manual. Cold Spring Harbor. NY: Cold Spring Harbor Laboratory Press; 1982
    Suche in Google Scholar
  • 17 Marchetti G, Patracchini P, Gemmati D, DeRosa V, Pinotti M, Rodorigo G, Casonato A, Girolami A, Bernardi F. Detection of two missense mutations and characterization of a repeat polymorphism in the factor VII gene (F7). Hum Genet 1992; 89: 497-502.
    PubMedSuche in Google Scholar
  • 18 Falanga A, Ofosu FA, Cortellazzo S, Delaini F, Consonni R, Caccia R, Longatti S, Maran D, Rodeghiero F, Pogliani E, Marassi A, D’Angelo A, Barbui T. Preliminary study to identify cancer patients at high risk of venous thrombosis following major surgery. Br J Haematol 1993; 85: 745-50.
    CrossrefPubMedSuche in Google Scholar
  • 19 Terwillinger JD, Ott J. Handbook of human genetic linkage. London: The J Hopkins University Press; 1994: 278-9.
    Suche in Google Scholar
  • 20 Stanton A. Glantz. Primer of biostatistics. New York: 1997. McGraw-Hill, Inc.;
    Suche in Google Scholar
  • 21 SAS Institute Inc. SAS/STAT User’s Guide, Version 6. Cary, NC: SAS Institute Inc; 1989
    PubMed
  • 22 Bernardi F, Arcieri P, Chiarotti F, Corral J, Pinotti M, Prydz H, Samama M, Sandset PM, Strom R, Vincente Garcia V, Mariani G. Contribution of factor VII genotype to activated FVII levels. Differences in genotype frequencies between Northern and Southern European populations. Arterioscl Thromb Vasc Biol 1997; 17: 2548-53.
    CrossrefPubMedSuche in Google Scholar
  • 23 de Maat MPM, Green F, de Knijff P, Jespersen G, Kluft C. Factor VII polymorphisms in populations with different risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 1997; 17: 1918-23.
    CrossrefPubMedSuche in Google Scholar
  • 24 de Knijff P, Green F, Johansen LG. et al. New alleles in F7 VNTR. Hum Mol Genet 1994; 3: 384.
    PubMedSuche in Google Scholar
  • 25 Lane A, Cruickshank JK, Mitchell J, Henderson A, Humphries S, Green F. Genetic and environmental determinants of factor VII coagulant activity in ethnic group at differing risk of coronary heart disease. Atherosclerosis 1992; 94: 43-50.
    CrossrefPubMedSuche in Google Scholar
  • 26 Pollak ES, Hung H-L, Godin W, Overton GC, High KA. Functional characterization of the human factor VII 5’-flanking region. J Biol Chem 1996; 271: 1738-47.
    CrossrefPubMedSuche in Google Scholar
  • 27 Dell’Acqua G, Iacoviello L, D’Orazio A, Di Castelnuovo A, Di Bitondo R, Donati MB. A polymorphic cluster in the 5’ region of the human coagulation factor VII gene: detection, frequency and linkage analysis. Thromb Res 1997; 88: 445-8.
    CrossrefPubMedSuche in Google Scholar
  • 28 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.
    CrossrefPubMedSuche in Google Scholar
  • 29 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 chracterized by angiography. Thromb Haemost 1996; 76: 161-5.
    Thieme ConnectPubMedSuche in Google Scholar
  • 30 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 Throm Vasc Biol 1997; 17: 2825-9.
    CrossrefPubMedSuche in Google Scholar
  • 31 Senapathy P, Shapiro MB, Harris NL. Splice junctions, branch point sites, and exons: sequence statistics, identification, and applications to genome project. Methods Enzymol 1990; 183: 252-78.
    PubMedSuche in Google Scholar
  • 32 Bernardi F, Patracchini P, Gemmati D. et al. Molecular analysis of factor VII deficiency in Italy: a frequent mutation (FVII Lazio) in a repeated intronic region. Hum Genet 1993; 92: 446-50.
    CrossrefPubMedSuche in Google Scholar
  • 33 Singal DP, Qiu X. Polymorphism in both X and Y box motifs controls level of expression of HLA-DRB1 genes. Immunogenetics 1996; 43: 50-6.
    PubMedSuche in Google Scholar
  • 34 Thompson EA, Deeb S, Walker D, Motulsky AG. The detection of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes. Am J Hum Genet 1988; 42: 113-24.
    PubMedSuche in Google Scholar
  • 35 Spek CA, Koster T, Rosendaal FR, Bertina RM, Reitsma PH. Genotypic variation in the promoter region of the protein C gene is associated with plasma protein C levels and thrombotic risk. Arterioscler Thromb Vasc Biol 1995; 15: 214-8.
    CrossrefPubMedSuche in Google Scholar
  • 36 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.
    Thieme ConnectPubMedSuche in Google Scholar
  • 37 Meilahn E, Ferrell R, Kiss J. et al. Genetic determination of coagulation factor VIIc levels among healthy middle-aged women. Thromb Haemost 1995; 73: 623-5.
    Thieme ConnectPubMedSuche in Google Scholar
  • 38 Heywood DM, Mansfield MW, Grant PJ. Factor VII polymorphisms, factor VII:c levels and features of insulin resistence in non-insulin-dependent diabetes mellitus. Thromb Haemost 1996; 75: 401.
    Thieme ConnectPubMedSuche in Google Scholar