Gene polymorphisms implicated in influencing susceptibility to venous and arterial thromboembolism: Frequency distribution in a healthy German population

Berthold Hoppe; Farzaneh Tolou; Thomas Dörner; Holger Kiesewetter; Abdulgabar Salama

doi:10.1160/TH06-06-0312

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2006; 96(04): 465-470
DOI: 10.1160/TH06-06-0312

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Gene polymorphisms implicated in influencing susceptibility to venous and arterial thromboembolism: Frequency distribution in a healthy German population

Authors

Berthold Hoppe

¹Institute of Transfusion Medicine, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Germany
Farzaneh Tolou

¹Institute of Transfusion Medicine, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Germany
Thomas Dörner

¹Institute of Transfusion Medicine, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Germany
Holger Kiesewetter

¹Institute of Transfusion Medicine, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Germany
Abdulgabar Salama

¹Institute of Transfusion Medicine, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Germany

Abstract

Summary

Evolvement and progression of cardiovascular diseases affecting the venous and arterial system are influenced bya multitude of environmental and hereditary factors. Many of these hereditary factors consist of defined gene polymorphisms, such as single nucleotide polymorphisms (SNPs) or insertion-deletion polymorphisms, which directly or indirectly affect the hemostatic system. The frequencies of individual hemostatic gene polymorphisms in different normal populations are well defined. However, descriptions of patterns of genetic variability of a larger extent of different factors of hereditary hypercoagulability in single populations are scarce. The aim of this study was i) to givea detailed description of the frequencies of factors of hereditary thrombophilia and their combinations in a German population (n = 282) and ii) to compare their distributions with those reported for other regions. Variants of coagulation factors [factor V 1691G>A (factor V Leiden), factor V 4070A>G (factor V HR2 haplotype), factor VII Arg353Gln, factor XIII Val34Leu, β-fibrinogen –455G>A, prothrombin 20210G>A], coagulation inhibitors [tissue factor pathway inhibitor 536C>T, thrombomodulin 127G>A], fibrinolytic factors [angiotensin converting enzyme intron 16 insertion/deletion, factor VII-activating protease 1601G>A (FSAP Marburg I), plasminogen activator inhibitor 1–675 insertion/deletion (5G/4G), tissue plasminogen activator intron h deletion/insertion], and other factors implicated in influencing susceptibility to thromboembolic diseases [apolipoprotein E2/E3/E4, glycoprotein Ia 807C>T, methylenetetrahydrofolate reductase 677C>T] were included. The distribution of glycoprotein Ia 807C>T deviated significantly from the Hardy- Weinberg equilibrium, and a comparison with previously published data indicates marked region and ethnicity dependent differences in the genotype distributions of some other factors.

Keywords

Thrombophilia - venous thromboembolism - atherothrombosis - SNP

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Referenzen

References
1 Bertina RM, Koeleman BP, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
2 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: 988-95.
3 Danckwardt S, Gehring NH, Neu-Yilik G. et al. The prothrombin 3’end formation signal reveals a unique architecture that is sensitive to thrombophilic gain-offunction mutations. Blood 2004; 104: 428-35.
4 Weisgraber KH, Rall Jr SC, Mahley RW. Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms. J Biol Chem 1981; 256: 9077-83.
5 Poort SR, Rosendaal FR, Reitsma PH. et al. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
6 Greenow K, Pearce NJ, Ramji DP. The key role of apolipoprotein E in atherosclerosis. J Mol Med 2005; 83: 329-42.
7 Ye Z, Liu EH, Higgins JP. et al. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 2006; 367: 651-8.
8 Folsom AR, Cushman M, Tsai MY. et al. A prospective study of venous thromboembolism in relation to factor V Leiden and related factors. Blood 2002; 99: 2720-5.
9 Carter AM, Catto AJ, Kohler HP. et al. alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism. Blood 2000; 96: 1177-9.
10 Faioni EM, Franchi F, Bucciarelli P. et al. Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (factor V Leiden). Blood 1999; 94: 3062-6.
11 Brouwer JL, Bijl M, Veeger NJ. et al. The contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus. Blood 2004; 104: 143-8.
12 Gerhardt A, Goecke TW, Beckmann MW. et al. The G20210A prothrombin-gene mutation and the plasminogen activator inhibitor (PAI-1) 5G/5G genotype are associated with early onset of severe preeclampsia. J Thromb Haemost 2005; 03: 686-91.
13 Prandoni P, Bilora F, Marchiori A. et al. An association between atherosclerosis and venous thrombosis. N Engl J Med 2003; 348: 1435-41.
14 Hoppe B, Tolou F, Radtke H. et al. MarburgI polymorphism of factor VII-activating protease is associated with idiopathic venous thromboembolism. Blood 2005; 105: 1549-51.
15 Franchi F, Martinelli I, Biguzzi E. et al. MarburgI polymorphism of factor VII-activating protease and risk of venous thromboembolism. Blood 2006; 107: 1731.
16 Hoppe B, Heymann GA, Koscielny J. et al. Screening for multiple hereditary hypercoagulability factors using the amplification refractory mutation system. Thromb Res 2003; 111: 115-20.
17 Green F, Kelleher C, Wilkes H. et al. A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals. Arterioscler Thromb 1991; 11: 540-6.
18 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.
19 Tybjaerg-Hansen A, Agerholm-Larsen B, Humphries SE. et al. A common mutation (G-455--> A) in the beta-fibrinogen promoter is an independent predictor of plasmafibrinogen, but not of ischemic heart disease. A study of 9,127 individuals based on the Copenhagen City Heart Study. J Clin Invest 1997; 99: 3034-9.
20 Kleesiek K, Schmidt M, Gotting C. et al. A first mutation in the human tissue factor pathway inhibitor gene encoding [P151L]TFPI. Blood 1998; 92: 3976-7.
21 Doggen CJ, Kunz G, Rosendaal FR. et al. A mutation in the thrombomodulin gene, 127G to A coding for Ala25Thr, and the risk of myocardial infarction in men. Thromb Haemost 1998; 80: 743-8.
22 Rigat B, Hubert C, Alhenc-Gelas F. et al. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990; 86: 1343-6.
23 Roemisch J, Feussner A, Nerlich C. et al. The frequent MarburgI polymorphism impairs the pro-urokinase activating potency of the factor VII activating protease (FSAP). Blood Coagul Fibrinol 2002; 13: 433-41.
24 Dawson SJ, Wiman B, Hamsten A. et al. The two allele sequences ofa common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem 1993; 268: 10739-45.
25 Ludwig M, Wohn KD, Schleuning WD. et al. Allelic dimorphism in the human tissue-type plasminogen activator (TPA) gene as a result of an Alu insertion/deletion event. Hum Genet 1992; 88: 388-92.
26 Kunicki TJ, Kritzik M, Annis DS. et al. Hereditary variation in platelet integrin alpha 2 beta1 density is associated with two silent polymorphisms in the alpha 2 gene coding sequence. Blood 1997; 89: 1939-43.
27 Goyette P, Sumner JS, Milos R. et al. Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification. Nat Genet 1994; 07: 551.
28 Rosendaal FR, Koster T, Vandenbroucke JP. et al. High risk of thrombosis in patients homozygous for factor V Leiden (activated proteinC resistance). Blood 1995; 85: 1504-8.
29 de Visser MC, Guasch JF, Kamphuisen PW. et al. The HR2 haplotype of factor V: effects on factor V levels, normalized activated protein C sensitivity ratios and the risk of venous thrombosis. Thromb Haemost 2000; 83: 577-82.
30 Bernardi F, Faioni EM, Castoldi E. et al. A factor V genetic component differing from factor V R506Q contributes to the activated proteinC resistance phenotype. Blood 1997; 90: 1552-7.
31 Martini CH, Doggen CJ, Cavallini C. et al. No effect of polymorphisms in prothrombotic genes on the risk of myocardial infarction in young adults without cardiovascular risk factors. J Thromb Haemost 2005; 03: 177-9.
32 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-4.
33 Elbaz A, Poirier O, Canaple S. et al. The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction. Blood 2000; 95: 586-91.
34 Catto AJ, Kohler HP, Coore J. et al. Association of a common polymorphism in the factor XIII gene with venous thrombosis. Blood 1999; 93: 906-8.
35 Iacoviello L, Di Castelnuovo A, De Knijff P. et al. Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction. N Engl J Med 1998; 338: 79-85.
36 Cambien F, Poirier O, Lecerf L. et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359: 641-4.
37 Eriksson P, Kallin B, van ’t Hooft FM. et al. Allelespecific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci USA 1995; 92: 1851-5.
38 Ridker PM, Baker MT, Hennekens CH. et al. Alurepeat polymorphism in the gene coding for tissue-type plasminogen activator (t-PA) and risks of myocardial infarction among middle-aged men. Arterioscler Thromb Vasc Biol 1997; 17: 1687-90.
39 Kluijtmans LA, den Heijer M, Reitsma PH. et al. Thermolabile methylenetetrahydrofolate reductase and factor V Leiden in the risk of deep-vein thrombosis. Thromb Haemost 1998; 79: 254-8.
40 Gerdes LU, Klausen IC, Sihm I. et al. Apolipoprotein E polymorphism in a Danish population compared to findings in 45 other study populations around the world. Genet Epidemiol 1992; 09: 155-67.
41 Tang Z, Tracy RP. Candidate genes and confirmed genetic polymorphisms associated with cardiovascular diseases: a tabular assessment. J Thromb Thrombolysis 2001; 11: 49-81.
42 Croft SA, Hampton KK, Sorrell JA. et al. The GPIa C807T dimorphism associated with platelet collagen receptor density is not a risk factor for myocardial infarction. Br J Haematol 1999; 106: 771-6.
43 Hoppe B, Heymann GA, Radtke H. et al. Association of MarburgI polymorphism of factor VII-activating protease with venous thromboembolism is limited to idiopathic events. Blood 2005; 105: 4899.
44 van Minkelen R, de Visser MC, Vos HL. et al. The Marburg I polymorphism of factor VII-activating protease is not associated with venous thrombosis. Blood 2005; 105: 4898.
45 Willeit J, Kiechl S, Weimer T. et al. MarburgI polymorphism of factor VII--activating protease: a prominent risk predictor of carotid stenosis. Circulation 2003; 107: 667-70.
46 Ireland H, Miller GJ, Webb KE. et al. The factor VII activating protease G511E (Marburg) variant and cardiovascular risk. Thromb Haemost 2004; 92: 986-92.
47 Santoso S, Kunicki TJ, Kroll H. et al. Association of the platelet glycoprotein Ia C807T gene polymorphism with nonfatal myocardial infarction in younger patients. Blood 1999; 93: 2449-53.
48 Gerhardt A, Scharf RE, Mikat-Drozdzynski B. et al. The polymorphism of platelet membrane integrin alpha2beta1 (alpha2807TT) is associated with premature onset of fetal loss. Thromb Haemost 2005; 93: 124-9.
49 Herrmann FH, Salazar-Sanchez L, Schröder W. et al. Prevalence of molecular risk factors FV Leiden, FV HR2, FII 20210G>A and MTHFR 677C>T in different populations and ethnic groups of Germany, Costa Rica and India. IJHG 2001; 01: 33-9.
50 Zivelin A, Mor-Cohen R, Kovalsky V. et al. Prothrombin 20210G>A is an ancestral prothrombotic mutation that occurred in whites approximately 24,000 years ago. Blood 2006; 107: 4666-8.