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Thromb Haemost 1998; 79(01): 8-13
DOI: 10.1055/s-0037-1614250
Review Article
Schattauer GmbH

Association of a Common Polymorphism in the Factor XIII Gene with Myocardial Infarction

Hans P. Kohler
1   From the Unit of Molecular Vascular Medicine, Leeds General Infirmary, Leeds, UK
,
Max H. Stickland
1   From the Unit of Molecular Vascular Medicine, Leeds General Infirmary, Leeds, UK
,
Nicholas Ossei-Gerning
1   From the Unit of Molecular Vascular Medicine, Leeds General Infirmary, Leeds, UK
,
Angela Carter
1   From the Unit of Molecular Vascular Medicine, Leeds General Infirmary, Leeds, UK
,
Hanna Mikkola
*   From the Department of Clinical Chemistry, University of Helsinki, Meilathi Hospital, Helsinki, Finland
,
Peter J. Grant
1   From the Unit of Molecular Vascular Medicine, Leeds General Infirmary, Leeds, UK
› Author Affiliations
Further Information

Publication History

Received 15 May 1997

Accepted after revision 20 August 1997

Publication Date:
08 December 2017 (online)

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Summary

Factor XIII when activated by thrombin, crosslinks fibrin, however its role in thrombotic disorders is unknown. A common point mutation (G T) in exon 2 of the A-subunit gene which codes for an amino acid change three amino acids from the thrombin activation site (Factor XIIIVal34Leu) is a candidate for a role in the pathogenesis of acute myocardial infarction. Factor XIII genotype frequencies were determined in a case-control study of 398 caucasian patients and 196 healthy controls. Patients had undergone angiography for investigation of coronary artery disease and were evaluated for a history of myocardial infarction. The prevalence of the mutation was lower in patients with myocardial infarction than without (32% vs. 50%), p = 0.0009 and than in controls (32% vs. 48%), p = 0.005. Patients possessing the mutation with a history of myocardial infarction had higher PAI-1 concentrations (mean, 27.9 vs. 16.7 ng/ml, p = 0.004) and the PAI-1 4G/4G genotype was commoner (43% vs. 26%, p = 0.03). There was no difference in PAI-1 4G/4G genotype (33% vs. 32%) and PAI-1 levels (mean, 21.0 vs. 20.9 ng/ml) in patients possessing wild type with MI compared to those without MI. These results indicate that the G T mutation coding for factor XIIIVal34Leu is protective against myocardial infarction and suggest a mechanism whereby elevated levels of PAI-1 may contribute to vascular risk.

 

  • References

  • 1 Grant PJ, Prentice CRM. Coronary Artery Disease. In: Haemostasis and Thrombosis.. Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. eds. Churchill Livingstone; Edinburgh and London: 02 1994: 1231-54.
    Google Scholar
  • 2 Fatah K, Silveira A, Tornvall P, Karpe F, Blombäck M, Hamsten A. Proneness to formation of tight and rigid fibrin gel structures in men with myocardial infarction at a young age.. Thromb Haemost 1996; 76: 535-40.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Fitzgerald DJ, Roy L, Catella F, Fitzgerald GA. Platelet activation in unstable coronary artery disease.. N Engl J Med 1986; 315: 983-9.
    CrossrefPubMedGoogle Scholar
  • 4 Davies MJ, Thomas A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death.. N Engl J Med 1984; 310: 1137-40.
    CrossrefPubMedGoogle Scholar
  • 5 Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes.. N Engl J Med 1992; 326: 242-50.
    CrossrefPubMedGoogle Scholar
  • 6 Jang Y, Lincoff AM, Plow EF, Topol EJ. Cell adhesion molecules in coronary artery disease.. J Am Coll Cardiol 1994; 24: 1591-601.
    CrossrefPubMedGoogle Scholar
  • 7 Landolfi R, De Cristofaro R, De Candia E, Rocco B, Bizzi B. Effect of fibrinogen concentration on the velocity of platelet aggregation.. Blood 1991; 78: 377-81.
    PubMedGoogle Scholar
  • 8 Aeschlimann D, Paulsson M. Transglutaminases: protein crosslinking enzymes in tissue and body fluids.. Thromb Haemost 1994; 71: 402-15.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Greenberg CS, Birckbichler PJ, Rice RH. Transglutaminases: multifunctional crosslinking enzymes that stabilize tissues.. FASEB J 1991; 5: 3071-7.
    CrossrefPubMedGoogle Scholar
  • 10 Lorand L, Losowsky MS, Miloszewski KJM. Human factor XIII fibrin stabilising factor.. Progress in Thrombosis and Haemostasis 1980; 5: 245-90.
    PubMedGoogle Scholar
  • 11 Schwarz ML, Pizzo SV, Hill RL, McKee PA. Human factor XIII from plasma and platelets. Molecular weights, subunit structures, proteolytic activation, and cross-linking of fibrinogen and fibrin.. J Biol Chem 1973; 248: 1359-407.
    PubMedGoogle Scholar
  • 12 Carrell NA, Erickson HP, McDonagh J. Electron microscopy and hydrodynamic properties of factor XIII subunits.. J Biol Chem 1989; 264: 551-6.
    PubMedGoogle Scholar
  • 13 Henriksson P, Becker S, Lynch B, McDonagh J. Identification of intracellular factor XIII in human monocytes and macrophages.. J Clin Invest 1985; 76: 528-34.
    CrossrefPubMedGoogle Scholar
  • 14 Sakata Y, Aoki N. Crosslinking of 2-antiplasmin inhibitor to fibrin by fibrin stabilizing factor.. J Clin Invest 1980; 65: 290-7.
    CrossrefPubMedGoogle Scholar
  • 15 Ichinose A, Davie EW. Characterization of the gene for the A subunit of human factor XIII (plasma transglutaminase), a blood coagulation factor.. Proc Natl Acad Sci USA 1988; 85: 5829-33.
    CrossrefPubMedGoogle Scholar
  • 16 Lewis SD, Lorand L, Fenton JW, Shafer JA. Catalytic competence of human - and -thrombin in the activation of fibrinogen and factor XIII.. Biochemistry 1987; 26: 7597-603.
    CrossrefPubMedGoogle Scholar
  • 17 Shen LL, Hermans J, McDonagh J, McDonagh RP, Carr M. Effects of calcium ion and covalent crosslinking on formation of elasticity of fibrin gels.. Thromb Res 1975; 6: 255-65.
    CrossrefPubMedGoogle Scholar
  • 18 Suzuki K, Iwata M, Ito S, Matsui K, Uchida A, Mizoi Y. Molecular basis for subtype differences of the “a” subunit of coagulation factor XIII with description of the genesis of the subtypes.. Hum Genet 1994; 94: 129-35.
    PubMedGoogle Scholar
  • 19 Anwar R, Stewart AD, Miloszewski KJA, Losowsky MS. Molecular basis of inherited factor XIII deficiency: identification of multiple mutations provides insights into protein function.. Brit J Haematol 1995; 91: 728-35.
    CrossrefPubMedGoogle Scholar
  • 20 Mikkola H, Syrjälä M, Rasi V, Vahtera E, Hamalainen E, Peltonen L, Palotie A. Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels.. Blood 1994; 84: 517-25.
    PubMedGoogle Scholar
  • 21 Suzuki K, Henke J, Iwata M, Henke L, Tsuji H, Fukunaga T, Ishimoto G, Szekelyi M, Ito S. Novel polymorphisms and haplotypes in the human coagulation factor XIII A-subunit gene.. Hum Genet 1996; 98: 393-5.
    CrossrefPubMedGoogle Scholar
  • 22 Kamura T, Okamura T, Murakawa M, Tsuda H, Teshima T, Shibuya T, Harada M, Niho Y. Deficiency of coagulation factor XIIIa subunit caused by dinucleotide deletion at the 5’-end of exon 3.. J Clin Invest 1992; 90: 315-9.
    CrossrefPubMedGoogle Scholar
  • 23 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens.. Acta Haematol 1957; 17: 237-46.
    CrossrefPubMedGoogle Scholar
  • 24 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: 731-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Yee VC, Pedersen LC, Trong IL, Bishop PD, Stenkamp RE, Teller DC. Three-dimensional structure of a transglutamase: human blood coagulation factor XIII.. Proc Natl Acad Sci USA 1994; 91: 7296-300.
    CrossrefPubMedGoogle Scholar
  • 26 Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain terminating inhibitors.. Proc Natl Acad Sci USA 1977; 74: 5463-7.
    CrossrefPubMedGoogle Scholar
  • 27 Carter AM, Mansfield MW, Stickland MH, Grant PJ. -Fibrinogen gene -455G/A polymorphism and fibrinogen levels.. Diabetes Care 1996; 19: 1265-8.
    CrossrefPubMedGoogle Scholar
  • 28 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: 842-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Shebuski RJ, Sitko GR, Claremon DA, Baldwin JJ, Remy DC, Stern AM. Inhibition of factor XIIIa in a canine model of coronary thrombosis: effect on reperfusion and acute reocclusion after recombinant tissue-type plasminogen activator.. Blood 1990; 7: 1455-9.
    PubMedGoogle Scholar
  • 30 Meade TW, Fellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WR, 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: 533-7.
    PubMedGoogle Scholar
  • 31 Hamsten A, de Faire U, Walldius G, Dahlen G, Szamosi A, Landou C, Blombäck M, Wiman B. Plasminogen activator inhibitor in plasma: Risk for recurrent myocardial infarction.. Lancet 1987; 2: 3-9.
    PubMedGoogle Scholar
  • 32 ECAT Angina Pectoris Study Group.. ECAT angina pectoris study: baseline association of haemostatic factors with extent of coronary arteriosclerosis and other coronary risk factors in 3000 patients with angina pectoris undergoing coronary angiography.. Eur Heart J 1993; 14: 8-17.
    PubMedGoogle Scholar
  • 33 Humphries S, Lane A, Dawson S, Green FR. The Study of Gene-Environment Interactions that Influence Thrombosis and Fibrinolysis – Genetic Variation at the Loci for Factor VII and Plasminogen Activator Inhibitor-1.. Arch Pathol Lab Med 1992; 116: 1322-9.
    PubMedGoogle Scholar
  • 34 Erikkson P, Kallin B, van’t Hooft F, Bavenholm P, Hamsten A. Allele specific increase in basal transcription of the plasminogen activator inhibitor-1 gene is associated with myocardial infarction.. Proc Natl Acad Sci USA 1995; 92: 1851-5.
    CrossrefPubMedGoogle Scholar