Factor XIII Val34Leu variant and the risk of myocardial infarction

Mona Shafey; Josdalyne L. Anderson; Dimitri Scarvelis; Steven P. Doucette; France Gagnon; Philip S. Wells

doi:10.1160/TH06-09-0517

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(04): 635-641
DOI: 10.1160/TH06-09-0517

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Factor XIII Val34Leu variant and the risk of myocardial infarction

A meta-analysis

Mona Shafey

¹Department of Medicine, University of Ottawa, Ontario, Canada

,

Josdalyne L. Anderson

²Ottawa Health Research Institute, Ontario, Canada

,

Dimitri Scarvelis

¹Department of Medicine, University of Ottawa, Ontario, Canada

,

Steven P. Doucette

²Ottawa Health Research Institute, Ontario, Canada

,

France Gagnon

⁴Department of Public Health Sciences, University of Toronto, Ontario, Canada

,

Philip S. Wells^*

¹Department of Medicine, University of Ottawa, Ontario, Canada

²Ottawa Health Research Institute, Ontario, Canada

³Department of Epidemiology and Community Medicine, University of Ottawa, Ontario, Canada

› Author Affiliations

Abstract

Summary

Genetic factors are thought to contribute to the pathogenesis of acute myocardial infarction (AMI).A common variant of factor XIII (FXIII), FXIII Val34Leu, may be protective against developing an AMI, but various studies show conflicting results. We performed a meta-analysis to determine whether the FXIII Val34Leu variant is associated with a decreased risk of AMI. One hundred ninety-five articles were reviewed and 12 case-control studies were selected. We included studies involving patients with objectively diagnosed AMIs (WHO criteria), provided that FXIII Val34Leu genotyping data were available. Inclusion decisions, quality assessment, and data extraction were conducted by two reviewers. Hypothesizing that the Leu allele was protective, we performed three analyses with the Val/Val genotype as the reference group. Pooled odds ratios (OR) and their 95% confidence intervals (95% CI) were determined. Prior to pooling, heterogeneity testing was performed using the I 2 statistic. These studies included a total of 8,743 patients, of which 3,663 were AMI patients and 5,080 were healthy controls. Using the random effects methods, protective effects were seen with the Leu/Val genotype alone (OR 0.79, 95% CI 0.68–0.93) and with Leu/Val and Leu/Leu genotypes combined (OR 0.79, 95% CI 0.66–0.93).There was also a protective effect with the Leu/Leu genotype alone, (not statistically significant: OR 0.83, 95% CI 0.61–1.12), likely due to the low frequency of this genotype. These results suggest that there is an association between the factor XIII Leu allele and a modest protective effect against AMI and may provide useful information in profiling susceptibility to myocardial infarction.

Keywords

Factor XIII - genetic - meta-analysis - myocardial infarction - risk factor

Full Text

References

References
1 Fuster V, Fallon JT, Nemerson Y. Coronary thrombosis. Lancet 1996; 348 (Suppl. 01) Suppl s7-s10.
2 Tegos TJ, Kalodiki E, Sabetai MM. et al. The genesis of atherosclerosis and risk factors: a review. Angiology 2001; 52: 89-98.
3 Lorand L, Losowsky MS, Miloszewski KJ. Human factor XIII: fibrin-stabilizing factor. Prog Hemost Thromb 1980; 5: 245-290.
4 Polgar J, Hidasi V, Muszbek L. Non-proteolytic activation of cellular protransglutaminase (placenta macrophage factor XIII). Biochem J 1990; 267: 557-560.
5 Schwartz ML, Pizzo SV, Hill RL. et al. Human factor XIII from plasma and platelets. Molecular weights, subunit structures, proteolytic activation, and crosslinking of fibrinogen and fibrin. J Biol Chem 1973; 248: 1395-1407.
6 Takagi T, Doolittle RF. Amino acid sequence studies on factor XIII and the peptide released during its activation by thrombin. Biochemistry 1974; 13: 750-756.
7 Shen L, Lorand L. Contribution of fibrin stabilization to clot strength. Supplementation of factor XIIIdeficient plasma with the purified zymogen. J Clin Invest 1983; 71: 1336-1341.
8 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.
9 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; 92: 2766-2770.
10 Attié-Castro FA, Zago MA, Lavinha J. et al. Ethnic heterogeneity of the Factor XIII Val34Leu polymorphism. Thromb Haemost 2000; 84: 601-603.
11 Balogh I, Szôke G, Karpati L. et al. Val34Leu polymorphism of plasma factor XIII: biochemistry and epidemiology in familial thrombophilia. Blood 2000; 96: 2479-2486.
12 Kohler HP, Whitaker P, Grant PJ. A common coding polymorphism in the FXIII A-subunit gene (FXIIIVal34Leu) affects cross-linking activity. Thromb Haemost 1998; 80: 704
13 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.
14 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 XIII V34L mutation. J Biol Chem 2000; 275: 20627-20631.
15 van Hylckama Vlieg A, Komanasin N, Ariëns RA. et al. Factor XIII Val34Leu polymorphism, factor XIII antigen levels and activity and the risk of deep venous thrombosis. Br J Haematol 2002; 119: 169-175.
16 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.
17 Breslow NE, Day NE. Statistical methods in cancer research. Volume I – The analysis of case-control studies. IARC Sci Publ 1980; 32: 5-338.
18 Attia J, Thakkinstian A, D'Este C. Meta-analyses of molecular association studies: Methodologic lessons for genetic epidemiology. J Clin Epidemiol 2003; 56: 297-303.
19 Sterne JA, Bradburn MJ, Egger M. Meta-analysis in Stata. In: Systematic Reviews in Health Care. Blackwell: BMJ Books; 2001: 347-369.
20 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558.
21 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188.
22 Petitti DB. Meta-analysis, decision analysis and cost-effectiveness analysis. New York NY: Oxford University Press; 1994
23 Aleksic N, Ahn C, Wang Y-W. et al. Factor XIIIA Val34Leu polymorphsim does not predict risk of coronary heart disease: the atherosclerosis risk in communities (ARIC) study. Arterioscler Thromb Vasc Biol 2002; 22: 348-352.
24 Bereczky Z, Czuriga E, Katona E. et al. Plasma factor XIII activity, concentration and FXIII – A Val34Leu polymorphism in patients with myocardial infarction and/or coronary stenosis. J Thromb Haemost 2003; 1: PO294 (Suppl. 01) Suppl Abstract
25 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.
26 Franco RF, Pazin-Filho A, Tavella MH. et al. Factor XIII val34leu and the risk of myocardial infarction. Haematologica 2000; 85: 67-71.
27 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.
28 Corral J, Gonzalez-Conejero R, Iniesta JA. et al. The FXIII Val34Leu polymorphism in venous and arterial thromboembolism. Haematologica 2000; 85: 293-297.
29 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.
30 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.
31 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.
32 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.
33 Atherosclerosis TaVBISG. No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age. Circulation 2004; 107: 1117-1122.
34 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.
35 Roldan V, Corral J, Marin F. et al. Role of factor XIII Val34Leu polymorphism in patients 45 years of age with acute myocardial infarction. Am J Cardiol 2003; 91: 1242-1245.
36 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.
37 Ioannidis JPA, Trikalinos TA, Ntzani EE. et al. Genetic associations in large versu small studies: an empirical assessment. Lancet 2003; 361: 567-71.
38 Casas JP, Hingorani AD, Bautista LE. et al. Metaanalysis of genetic studies in ischemic strokes: thirtytwo genes involving approximately 18, 000 cases and 58,000 controls. Arch Neurol 2004; 61: 1652-61.
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 Little JA, Bradley L, Bray MS. et al. Reporting, Appraising, and integrating data on genotype prevalence and gene-disease association studies. Am J Epidemiol 2002; 156: 300-310.