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Thromb Haemost 2008; 99(06): 1085-1089
DOI: 10.1160/TH07-12-0755
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Factor XIII Val34Leu polymorphism and the risk of myocardial infarction under the age of 36 years

Loukianos S. Rallidis
1   Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece
,
Marianna Politou
2   Laboratory of Haematology and Blood Transfusion Unit, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece
,
Christoforos Komporozos
1   Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece
,
Demosthenes B. Panagiotakos
3   Department of Nutrition Science – Dietetics, Harokopio University, Athens, Greece
,
Chrisoula I. Belessi
4   Department of Haematology, General Hospital of Hospital of Nikea, Piraeus, Greece
,
Anthi Travlou
2   Laboratory of Haematology and Blood Transfusion Unit, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece
,
John Lekakis
1   Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece
,
Dimitrios T. Kremastinos
1   Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece
› Author Affiliations
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Publication History

Received 27 December 2007

Accepted after major revision 31 March 2008

Publication Date:
27 November 2017 (online)

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Summary

There are limited and controversial data regarding the impact of factor XIII (FXIII) Val34Leu polymorphism in the pathogenesis of premature myocardial infarction (MI). We examined whether FXIII Val34Leu polymorphism is associated with the development of early MI.We recruited 159 consecutive patients who had survived their first acute MI under the age of 36 years (mean age=32.1 ± 3.6 years, 138 were men). The control group consisted of 121 healthy individuals matched with cases for age and sex, without a family history of premature coronary heart disease (CHD). FXIII Val34Leu polymorphism was tested with polymerase chain reaction and reverse hybridization. There was a lower prevalence of carriers of the Leu34 allele in patients than in controls (30.2 vs. 47.1%, p=0.006). FXIII Val34Leu polymorphism was associated with lower risk for acute MI after adjusting for major cardiovascular risk factors (odds ratio [OR] = 0.51, 95% confidence interval [CI] 0.27–0.95, p=0.03). Subgroup analysis according to angiographic findings (“normal” coronary arteries [n=29] or significant CHD [n=130]) showed that only patients with MI and significant CHD had lower prevalence of carriers of the Leu34 allele compared to controls after adjusting for major cardiovascular risk factors (OR = 0.42, 95% CI 0.22–0.83, p=0.01). Our data indicate that FXIII Val34Leu polymorphism has a protective effect against the development of MI under the age of 36 years, particularly in the setting of significant CHD.

Keywords

Factor XIII Val34Leu polymorphism - premature myocardial infarction - risk factors
 

  • References

  • 1 Rosendaal FR, Siscovick DS, Schwartz SM. et al. A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood 1997; 90: 1747-1750.
    PubMedGoogle Scholar
  • 2 Ardissino D, Mannucci PM, Merlini PA. et al. Prothrombotic genetic risk factors in young survivors of myocardial infarction. Blood 1999; 94: 46-51.
    PubMedGoogle Scholar
  • 3 Rallidis LS, Belesi CI, Manioudaki HS. et al. Myocardial infarction under the age of 36: prevalence of thrombophilic disorders. Thromb Haemost 2003; 90: 272-278.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Muszbek L, Yee VC, Hevessy Z. Blood coagulation factor XIII: structure and function. Thromb Res 1999; 94: 271-305.
    CrossrefPubMedGoogle Scholar
  • 5 de Lange M, Andrew T, Snieder H. et al. Joint linkage and association of six single-nucleotide polymorphisms in the factor XIII-A subunit gene point to V34L as the main functional locus. Arterioscler Thromb Vasc Biol 2006; 26: 1914-1919.
    CrossrefPubMedGoogle Scholar
  • 6 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.
    CrossrefPubMedGoogle Scholar
  • 7 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.
    CrossrefPubMedGoogle Scholar
  • 8 Shafey M, Anderson JL, Scarvelis D. et al. Factor XIII Val34Leu variant and the risk of myocardial infarction: a meta-analysis. Thromb Haemost 2007; 97: 635-641.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Vokó Z, Bereczky Z, Katona E. et al. Factor XIII Val34Leu variant protects against coronary artery disease. A meta-analysis. Thromb Haemost 2007; 97: 458-463.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Hancer VS, Diz-Kucukkaya R, Bilge AK. et al. The association between Factor XIII polymorphism and early myocardial infarction. Circ J 2006; 70: 239-242.
    CrossrefPubMedGoogle Scholar
  • 11 Franco RF, Pazin-Filho A, Tavella MH. et al. Factor XIII val34leu and the risk of myocardial infarction. Haematologica 2000; 85: 67-71.
    PubMedGoogle Scholar
  • 12 Roldán V, Corral J, Marín 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.
    CrossrefPubMedGoogle Scholar
  • 13 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.
    CrossrefPubMedGoogle Scholar
  • 14 Roldán V, González-Conejero R, Marín F. et al. Five prothrombotic polymorphisms and the prevalence of premature myocardial infarction. Haematologica 2005; 90: 421-423.
    PubMedGoogle Scholar
  • 15 Nomenclature and criteria for diagnosis of ischemic heart disease. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation 1979; 59: 607-609.
    CrossrefPubMedGoogle Scholar
  • 16 Ariëns 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.
    PubMedGoogle Scholar
  • 17 Rubens FD, Perry DW, Hatton MW. et al. Platelet accumulation on fibrin-coated polyethylene: role of latelet activation and factor XIII. Thromb Haemost 1995; 73: 850-856.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Choudhury I, Marsh JD. Myocardial infarction in young patients. Am J Med 1999; 107: 254-261.
    CrossrefPubMedGoogle Scholar
  • 19 Kardasz I, De Caterina R. Myocardial infarction with normal coronary arteries: a conundrum with multiple aetiologies and variable prognosis: an update. J Intern Med 2007; 261: 330-348.
    CrossrefPubMedGoogle Scholar
  • 20 Speidl WS, Nikfardjam M, Niessner A. et al. Premature compared with late onset of coronary artery disease: young patients show a severe defect in fibrinolytic response to venous occlusion. Blood Coagul Fibrinolysis 2007; 18: 165-171.
    CrossrefPubMedGoogle Scholar
  • 21 Sozzi FB, Danzi GB, Foco L. et al. Myocardial infarction in the young: a sex-based comparison. Coron Artery Dis 2007; 18: 429-431.
    CrossrefPubMedGoogle Scholar
  • 22 Verheugt FW, ten Cate JW, Sturk A. et al. Tissue plasminogen activator activity and inhibition in acute myocardial infarction and angiographically normal coronary arteries. Am J Cardiol 1987; 59: 1075-1079.
    CrossrefPubMedGoogle Scholar
  • 23 Voetsch B, Loscalzo J. Genetic determinants of arterial thrombosis. Arterioscler Thromb Vasc Biol 2004; 24: 216-229.
    CrossrefPubMedGoogle Scholar
  • 24 Mannila MN, Eriksson P, Ericsson CG. et al. Epistatic and pleiotropic effects of polymorphisms in the fibrinogen and coagulation factor XIII genes on plasma fibrinogen concentration, fibrin gel structure and risk of myocardial infarction. Thromb Haemost 2006; 95: 420-427.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 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.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Lim BC, Ariëns 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.
    CrossrefPubMedGoogle Scholar
  • 27 Bereczky Z, Balogh E, Katona E. 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; 120: 567-573.
    CrossrefPubMedGoogle Scholar