Coagulation Factor XIII and Cardiovascular Disease in UK Asian Patients Undergoing Coronary Angiography

Summary

Possession of the coagulation factor XIII Val34Leu (FXIIIVal34Leu) polymorphism is associated with protection against myocardial infarction (MI) in Caucasians, in the absence of features of insulin resistance. The role of this polymorphism in the UK Asian population, with its high prevalence of insulin resistance and ischaemic heart disease, is unknown. We investigated the frequency of genotypes at this polymorphism, and measures of circulating FXIII in a group of UK Asians attending for coronary angiography. Genotype at the FXIIIVal34Leu polymorphism was not associated with MI. FXIII B-subunit levels correlated with waist: hip ratio (r = 0.19, p 0.005), HbA1c (r = 0.18, p 0.05), fasting triglycerides (r = 0.21, p 0.005), total cholesterol (r = 0.29, p 0.0005) and PAI-1 antigen (r = 0.24, p 0.005). An association between FXIIIVal34Leu and FXIII cross-linking activity was confirmed in these subjects (one-way ANOVA p 0.0005). This evidence does not support the hypothesis that FXIIIVal34Leu is protective against MI in the UK Asian population. FXIII B-subunit levels are strongly linked to risk factors for cardiovascular disease, suggesting an underlying association with insulin resistance.

Keywords

Polymorphism - ethnicity - cardiovascular disease - factor XIII - risk factors

• References

• 1 Lóránd L, Losowsky MS, Miloszewski KJM. Human factor XIII: fibrin stabilising factor. Prog Thromb Haemost 1980; 5: 245-90.
• 2 Greenberg CS, Birckbichler PJ, Rice RH. Transglutaminases: multifunctional crosslinking enzymes that stabilize tissues. FASEB J 1991; 5: 3071-7.
• 3 Carr ME, Gabriel DA, McDonagh J. Influence of factor XIII and fibronectin on fiber size and density in thrombin-induced fibrin gels. J Lab Clin Med 1987; 110: 747-52.
• 4 Mosher DF, Schad PE, Kleinman HK. Cross-linking of fibronectin to collagen by blood coagulation factor XIIIa. J Clin Invest 1979; 64: 781-7.
• 5 Schwarz ML, Pizzo SV, Hill RL, McKee PA. Human factor XIII from plasma and platelets. Molecular weights, subunit structures, proteolytic activation, and crosslinking of fibrinogen and fibrin. J Biol Chem 1973; 248: 1359-407.
• 6 Chung SI, Lewis MS, Folk JE. Relationships of the catalytic properties of human plasma and platelet transglutaminases (Activated blood coagulation factor XIII) to their subunit structures. J Biol Chem 1974; 249: 940-50.
• 7 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.
• 8 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.
• 9 Kohler HP, Mansfield MW, Clark PS, Grant PJ. Interaction between insulin resistance and factor XIIIVal34Leu in patients with coronary artery disease. Thromb Haemost 1999; 82: 1202-3.
• 10 Kohler HP, Ariëns RAS, Whitaker P, Grant PJ. A common coding polymorphism in the FXIII A-subunit gene (FXIIIVAL34LEU) affects cross-linking activity. Thromb Haemost 1998; 80: 704.
• 11 Ariens RAS, Phillipou H, Nagaswami C, Weisel JW, Lane DA, Grant PJ. The Factor XIII V34L polymorphism accelerates thrombin activation of Factor XIII and affects cross-linked fibrin structure. Blood 2000; 96: 988-5.
• 12 Ichinose A, Tsukamoto H, Izumi T, Yamazaki T, Togashi M, Takamatsu J, Saito H, Umeyama H. Arg260-Cys mutation in severe factor XIII deficiency: conformational change of the A subunit is predicted by molecular modelling and mechanics. Br J Haematol 1998; 101: 264-72.
• 13 Izumi T, Nagaoka U, Saito T, Takamatsu J, Saito H, Ichinose A. Novel deletion and insertion mutations cause splicing defects, leading to severe reductuion in mRNA levels of the A subunit in severe factor XIII deficiency. Thromb Haemost 1998; 79: 479-85.
• 14 Donaldson LJ, Taylor JB. Patterns of Asian and non-Asian morbidity in hospitals. Br Med J 1983; 286: 949-51.
• 15 Marmot MG, Adelstein AM, Bulusu L. Immigrant mortality in England and Wales 1970-1978. OCPS Studies of Medical and Population Subjects no. 47. London: HMSO; 1984
• 16 Balarajan R, Bulusu L, Adelstein AM, Shukla V. Patterns of mortality among migrants to England and Wales from the Indian subcontinent. Br Med J 1984; 289: 1185-7.
• 17 McKeigue PM, Marmot MG. Mortality from coronary heart disease in Asian communities in London. Br Med J 1988; 297: 903.
• 18 Hughes LO, Raval U, Raftery EB. Coronary disease in Asians: an ethnic problem. Br Med J 1989; 298: 1340-5.
• 19 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-46.
• 20 Kohler HP, Futers TS, Grant PJ. Prevalence of three common polymorphisms in the A-subunit gene of factor XIII in patients with coronary artery disease: association with FXIII activity and antigen levels. Thromb Haemost 1999; 81: 511-5.
• 21 Kangsadalampai S, Board PG. The Val34Leu polymorphism in the A subunit of coagulation factor XIII contributes to the large normal range in activity and demonstrates that the activation peptide plays a role in catalytic activity. Blood 1998; 8: 2766-70.
• 22 McCormack L, Kain K, Kohler HP, Grant PJ. Prevalence of FXIIIVal34Leu in populations with different cardiovascular risk. Thromb Haemost 1998; 80: 523-4.
• 23 Mansfield MW, Kohler HP, Ariëns RAS, McCormack L, Grant PJ. Circulating levels of coagulation factor XIII in subjects with type 2 diabetes mellitus and their first-degree relatives. Diabetes Care 2000; 23: 703.
• 24 McKeigue PM, Shah B, Marmot MG. Prevalence of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet 1991; 337: 382-6.
• 25 Ashwell M, Cole TJ, Dixon AK. Obesity: new insight into the anthropometric classification of fat distribution shown by computed tomography. Br Med J 1985; 200: 1692-4.
• 26 Trumbo TA, Maurer MC. Examining thrombin hydrolysis of the Factor XIII activation peptide segment leads to a proposal for explaining the cardioprotective effects observed with the Factor XIIIVal34Leu mutation. J Biol Chem 2000; 275 (Suppl. 27) 20627-31.