Prevalence of Three Common Polymorphisms in the A-subunit Gene of Factor XIII in Patients with Coronary Artery Disease

Summary

Activated blood coagulation factor XIII has an important role in the final stage of the clotting cascade by the covalent crosslinking of α- and γ-fibrin chains. We have recently shown that a functional polymorphism in exon 2, codon 34 of the FXIII A-subunit gene is protective against myocardial infarction. To investigate the prevalence of three other common point mutations in the A-subunit gene (codon 564, C to T, 650 G to A and 651 G to C) and their association with FXIII activity and antigen levels, 275 patients with coronary artery disease and 196 controls were studied. There was no difference in the prevalence of the polymorphisms between patients and controls or between patients with or without MI. Only genotype at codon 564 was associated with FXIII activity with lower activities in subjects possessing the T allele. There was evidence of linkage disequilibrium between codon 34 and codon 564. These results suggest that FXIIIVal34Leu is the only common polymorphism in the coding region of the A-subunit gene of FXIII associated with coronary artery disease.

• References

• 1 Greenberg CS, Birckbichler PJ, Rice RH. Transglutaminases: multifunctional crosslinking enzymes that stabilize tissues. FASEB J 1991; 5: 3071-7.
• 2 Lorand L, Losowsky MS, Miloszewski KJM. Human factor XIII fibrin stabilising factor. Progr Thromb Haemost 1980; 5: 245-90.
• 3 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.
• 4 Carell NA, Erickson HP, McDonagh J. Electron microscopy and hydrodynamic properties of factor XIII subunits. J Biol Chem 1989; 264: 551-6.
• 5 Kloczko J, Wojtukiewicz M, Bielawiec M, Zarzycka B, Kinalska I. Plasma factor XIII and some other haemostasis parameters in patients with diabetic angiopathy. Acta Haemat 1986; 76: 81-5.
• 6 Kloczko J, Wojtukiewicz M, Bielawiec M, Zuch A. Alterations of haemostasis parameters with special reference to fibrin stabilization, factor XIII and fibronectin in patients with obliterative atherosclerosis. Thromb Res 1988; 51: 575-81.
• 7 Francis CW, Connaghan DG, Scott WL, Marder VJ. Increased plasma concentration of cross-linked fibrin polymers in acute myocardial infarction. Circulation 1987; 6: 1170-7.
• 8 Kohler HP, Stickland MH, Ossei-Gerning N, Carter A, Mikkola H, Grant PJ. Association of a common polymorphism in the factor XIII gene with myocardial infarction. Thromb Haemost 1998; 79: 8-13.
• 9 Catto AJ, Kohler HP, Coore J, Mansfield MW, Stickland MH, Grant PJ. Association of a common polymorphism in the factor XIII gene with venous thrombosis. Blood 1999; 93: 906-8.
• 10 Catto AJ, Kohler HP, Bannan S, Stickland MH, Carter A, Grant PJ. Factor XIIIVal34Leu: a novel association with primary intracerebral haemorrhage. Stroke 1998; 29: 813-6.
• 11 McCormack LJ, Kain K, Catto AJ, Kohler HP, Stickland MH, Grant PJ. Prevalence of FXIII V34L in populations with different cardiovascular risk. Thromb Haemost 1998 [letter]. Thromb Haemost 1998; 80: 523-4.
• 12 Kohler HP, Ariens RAS, Whitaker P, Grant PJ. A common coding polymorphism in the FXIII A-subunit gene (FXIIIVal34Leu) affects cross-linking activity. Thromb Haemost 1998 [letter]. Thromb Haemost 1998; 80: 704
• 13 Kohler HP, Ariens RAS, Mansfield MW, Whitaker P, Grant PJ. Factor XIII activity and antigen levels in patients with coronary artery disease: interaction with FXIIIVal34Leu. Eur Heart J 1998; 19 Suppl 579. [abstract]
• 14 Suzuki K, Iwata M, Ito S, Matsui K, Uchida A, Mizoi Y. Molecular basis for subtypic differences of the A-subunit of coagulation factor XIII with description of the genesis of the subtypes. Hum Genet 1994; 94: 129-35.
• 15 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.
• 16 Anwar R, Stewart AD, Miloszewski KJA, Losowsky MS. Molecular basis of inherited factor XIII deficiency: identification of multiple mutations provides insights into protein function. Br J Haematol 1995; 91: 728-35.
• 17 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 mutations demonstrate different effects on transcript levels. Blood 1994; 84: 517-25.
• 18 Weir B, Cockerham C. Estimation of linkage disequilibrium in randomly mating populations. Heredity 1979; 24: 105-11.
• 19 Baumann R, Henschen A. Linkage disequilibrium relationship among four polymorphisms within the human fibrinogen gene cluster. Hum Genet 1994; 94: 165-70.
• 20 Board PG. Genetic polymorphism of the A subunit of human coagulation factor XIII. Am J Hum Genet 1979; 31: 116-24.
• 21 Suzuki K, Matsui K, Ito S, Fujita K, Matsumoto H. Polymorphism of the A-subunit of coagulation factor XIII: evidence for subtypes of the FXIIIA*1 and FXIIIA*2 alleles. Am J Hum Genet 1988; 43: 170-4.
• 22 Ichinose A, Davie E. Characterisation of the gene for the a subunit of human factor XIII (plasma transglutaminase), a blood coagulation factor. Proc Natl Acad Sci USA 1986; 85: 5829-33.
• 23 Yee VC, Pedersen LC, Trong IL, Bishop PD, Stenkamp RE, Teller DC. Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII. Proc Natl Acad Sci USA 1994; 91: 7296-300.