Factor XIII Val34Leu variant protects against coronary artery disease

Summary

Several studies suggested that Val34Leu variant of factor XIII (FXIII) might have a protective effect against coronary artery disease (CAD), but studies not supporting these findings have also been published. The authors performed a meta-analysis of 16 studies on 5,346 cases and 7,053 controls that investigated the association between Val34Leu polymorphism and CAD defined as history of myocardial infarction or significant stenosis on a coronary artery assessed by coronary angiography. Because of the heterogeneity of the study-specific results, the pooled effect estimates were calculated by a random-effects empirical Bayes model. The combined odds ratios for CAD were 0.82 (95% confidence interval [95% Cl] 0.73, 0.94) for the heterozygotes of the FXIIIVal34Leu variant, 0.89 (95% CI 0.69, 1.13) for the homozygotes, and 0.81 (95% CI 0.70, 0.92) for the heterozygotes and homozygotes combined. The results were essentially the same when only myocardial infarction was considered as outcome. The beneficial effect of the polymorphism might be smaller than the effect estimates obtained in this metaanalysis, because the analysis raised the possibility of publication bias. Data published in the literature suggest that gene-gene and gene-environmental interactions might significantly influence the protective effect of FXIII-AVal34Leu polymorphism.

Keywords

Coronary disease - factor XIII - polymorphism - meta-analysis

• References

• 1 Muszbek L, Adany R, Mikkola H. Novel aspects of blood coagulation factor XIII. I. Structure, distribution, activation, and function. Crit Rev Clin Lab Sci 1996; 33: 357-421.
• 2 Mikkola H, Syrjala M, Rasi V. et al. Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels. Blood 1994; 84: 517-525.
• 3 Balogh I, Szoke G, Karpati L. et al. Val34Leu polymorphism of plasma factor XIII: biochemistry and epidemiology in familial thrombophilia. Blood 2000; 96: 2479-2486.
• 4 Wartiovaara U, Mikkola H, Szoke G. et al. Effect of Val34Leu polymorphism on the activation of the coagulation factor XIII-A. Thromb Haemost 2000; 84: 595-600.
• 5 Ariens RA, Philippou H, Nagaswami C. et al. The factor XIII V34L polymorphism accelerates thrombin activation of factor XIII and affects cross-linked fibrin structure. Blood 2000; 96: 988-995.
• 6 Lim BC, Ariens RA, Carter AM. et al. Genetic regulation of fibrin structure and function: complex gene-environment interactions may modulate vascular risk. Lancet 2003; 361: 1424-1431.
• 7 Wells PS, Anderson JL, Scarvelis DK. et al. Factor XIII Val34Leu variant is protective against venous thromboembolism: a HuGE review and meta-analysis. Am J Epidemiol 2006; 164: 101-109.
• 8 Kohler HP, Stickland MH, Ossei-Gerning N. et al. Association of a common polymorphism in the factor XIII gene with myocardial infarction. Thromb Haemost 1998; 79: 8-13.
• 9 Wartiovaara U, Perola M, Mikkola H. et al. Association of FXIII Val34Leu with decreased risk of myocardial infarction in Finnish males. Atherosclerosis 1999; 142: 295-300.
• 10 Canavy I, Henry M, Morange PE. et al. Genetic polymorphisms and coronary artery disease in the south of France. Thromb Haemost 2000; 83: 212-216.
• 11 Corral J, Gonzalez-Conejero R, Iniesta JA. et al. The FXIII Val34Leu polymorphism in venous and arterial thromboembolism. Haematologica 2000; 85: 293-297.
• 12 Franco RF, Pazin-Filho A, Tavella MH. et al. Factor XIII val34leu and the risk of myocardial infarction. Haematologica 2000; 85: 67-71.
• 13 Gemmati D, Serino ML, Ongaro A. et al. A common mutation in the gene for coagulation factor XIII-A (Val34Leu): a risk factor for primary intracerebral hemorrhage is protective against atherothrombotic diseases. Am J Hematol 2001; 67: 183-188.
• 14 Warner D, Mansfield MW, Grant PJ. Coagulation factor XIII and cardiovascular disease in UK Asian pa- tients undergoing coronary angiography. Thromb Haemost 2001; 85: 408-411.
• 15 Aleksic N, Ahn C, Wang YW. et al. Factor XIIIA Val34Leu polymorphism does not predict risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vasc Biol 2002; 22: 348-352.
• 16 Kakko S, Elo T, Tapanainen JM. et al. Polymorphisms of genes affecting thrombosis and risk of myocardial infarction. Eur J Clin Invest 2002; 32: 643-648.
• 17 Reiner AP, Frank MB, Schwartz SM. et al. Coagulation factor XIII polymorphisms and the risk of myocardial infarction and ischaemic stroke in young women. Br J Haematol 2002; 116: 376-382.
• 18 Doggen CJ, Reiner AP, Vos HL et al. Two factor XIII gene polymorphisms associated with a structural and functional defect and the risk of myocardial infarction in men. J Thromb Haemost 2003; 1: 2056-2058.
• 19 Reiner AP, Heckbert SR, Vos HL. et al. Genetic variants of coagulation factor XIII, postmenopausal estrogen therapy, and risk of nonfatal myocardial infarction. Blood 2003; 102: 25-30.
• 20 Atherosclerosis, Thrombosis, and Vascular Biology Italian Study Group. No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age. Circulation 2003; 107: 1117-1122.
• 21 Butt C, Zheng H, Randell E. et al. Combined carrier status of prothrombin 20210A and factor XIII-A Leu34 alleles as a strong risk factor for myocardial infarction: evidence of a gene-gene interaction. Blood 2003; 101: 3037-3041.
• 22 Roldan V, Corral J, Marin F. et al. Role of factor XIII Val 34 Leu polymorphism in patients <45 years of age with acute myocardial infarction. Am J Cardiol 2003; 91: 1242-1245.
• 23 Hancer VS, Diz-Kucukkaya R, Bilge AK et al. The association between factor XIII Val34Leu polymorphism and early myocardial infarction. Circ J 2006; 70: 239-242.
• 24 Marin F, Roldan V, Sogor F. Factor XIII Val34Leu polymorphism and premature myocardial infarction. (Spanish) Rev Esp Cardiol 2002; 55: 1106-1107.
• 25 Boekholdt SM, Sandhu MS, Wareham NJ. et al. Fibrinogen plasma levels modify the association between the factor XIII Val34Leu variant and risk of coronary artery disease: the EPIC-Norfolk prospective population study. J Thromb Haemost 2006; 4: 2204-2209.
• 26 Odeberg J, Freitag M, Odeberg H. et al. Severity of acute coronary syndrome is predicted by interactions between fibrinogen concentrations and polymorphisms in the GPIIIa and FXIII genes. J Thromb Haemost 2006; 4: 909-912.
• 27 Bereczky Zs, Balogh E, Katona É. et al. Modulation of the risk of coronary sclerosis/myocardial infarction by the interaction between factor XIII subunit A Val34Leu polymorphism and fibrinogen concentration in the high risk Hungarian population. Thromb Res. 2007 doi:10.1016/j.thromres.2006.12.013
• 28 World Health Organization. Manual of the International Classification of Disease, Injuries and Causes of Death, Volume 1, 9^th revision. Geneva: WHO; 1977
• 29 Rothman KJ. Modern epidemiology. 1st ed. Boston: Little, Brown and Company, 1986; 145-146.
• 30 Cochran WG. The combination of estimates from different experiments. Biometrics 1954; 10: 101-129.
• 31 Sutton AJ, Abrams KR, Jones DR. et al. Methods for meta-analysis in medical research. Chicester: John Wiley & Sons Ltd; 2006
• 32 Stata Statistical Software: Release 9. College Station, Texas: Stata Corp LP, 2005
• 33 Stata Technical Bulletin Reprints: Volume 7. College Station, Texas: Stata Corp LP, 1998; 100–108
• 34 Egger M, Davey SG, Schneider M. et al. Bias in meta-analysis detected by a simple, graphical test. Br Med J 1997; 315: 629-634.
• 35 Stata Technical Bulletin Reprints: Volume 7. College Station, Texas: StataCorp LP, 1998: 125–133
• 36 Rothman KJ, Greenland S. Modern epidemiology. 2nd ed. Philadelphia: Lipincott-Raven Publishers; 1998: 9-11.
• 37 McKee M, Zatonski W. How the cardiovascular burden of illness is changing in eastern Europe. Evid Based Cardiovasc Med 1998; 2: 39-41.
• 38 Kobbervig C, Williams E. FXIII polymorphisms, fibrin clot structure and thrombotic risk. Biophys Chem 2004; 112: 223-228.
• 39 Kohler HP, Mansfield MW, Clark PS. et al. Interaction between insulin resistance and factor XIII Val34Leu in patients with coronary artery disease. Thromb Haemost 1999; 82: 1202-1203.
• 40 Rubens FD, Perry DW, Hatton MW. et al. Platelet accumulation on fibrin-coated polyethylene: role of platelet activation and factor XIII. Thromb Haemost 1995; 73: 850-856.
• 41 Harsfalvi J, Legrand C, Muszbek L. Platelet adhesion to FXIII-cross-linked fibrin at static and dynamic conditions. Thromb Haemost. 1997 Suppl: S124 (abstract)
• 42 Rothman K, Greenland S. Modern Epidemiology. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 1998: 286-287.