RSS-Feed abonnieren
DOI: 10.1160/TH02-12-0305
Allele 4G of gene PAI-1 associated with prothrombin mutation G20210A increases the risk for venous thrombosis
Publikationsverlauf
Received
06. Dezember 2002
Accepted after resubmission
07. August 2003
Publikationsdatum:
05. Dezember 2017 (online)
Summary
Several studies have tried to clarify the role of polymorphism 4G/5G of the PAI-1 gene in venous thromboembolism without reaching any final conclusion. It has been demonstrated that this polymorphism may induce an increased risk for venous thromboembolism (VTE) in patients with thrombophilic defects. We studied the association of prothrombin mutation G20210A with 4G/5G polymorphism in 402 VTE patients and 466 healthy controls. Patients affected by prothrombin mutation G20210A, with or without the concomitant presence of allele 4G, had a 3.7 thrombotic risk (C.I. 95% 2.3–6.0; p<0.0001). Moreover, genotype 4G/4G is a mild risk factor for VTE, irrespectively of whether the prothrombin mutation was present.
Logistic regression analysis showed that patients carrying the G20210A prothrombin mutation with allele 4G gave an odds ratio for VTE of 6.1 (C.I. 95% 3.2 – 11.4; p<0.001). The risk increased up to 13.0 (C.I. 95% 3.0 – 60.4; p<0.001) when we considered the association of the prothrombin mutation with genotype 4G/4G. The G20210A mutation without allele 4G (5G/5G) was not a risk factor for VTE. In conclusion, we believe that patients affected by VTE with concomitant presence of the G20210A prothrombin mutation could be tested for genotype 4G/4G to better define their thrombotic risk.
-
References
- 1 Ny T, Sawdey M, Lawrence D. et al. Cloning and sequence of a cDNA coding for the human beta-migrating-endothelial-cell-type plasminogen activator inhibitor. Proc Natl Acad Sci USA 1986; 83: 6776-80.
- 2 Dawson S, Wiman B, Hamsten A. et al. The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor (PAI-1) gene respond differently to interleukin-1 in hepG2 cell. J Biol Chem 1993; 268: 10739-745.
- 3 Eriksson P, Kalling B, van’t Hooft FM. et al. Allele-specific increase in basal transcription of the plasminogen activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci U S A 1995; 92: 1851-55.
- 4 Kohler HP, Grant PJ. Plasminogen-Activator Inhibitor type I and coronary artery disease. New Engl J Med 2000; 342: 1792-801.
- 5 Hamsten A, Wiman B, de Faire U, Blomback M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. New Engl J Med 1985; 313: 1157-63.
- 6 Mansfield MW, Stikland MH, Grant PJ. Plasminogen activator inhibitor-1 (PAI-1) promoter polymorphism and coronary artery disease in Non-Insulin-Dependent Diabetes. Thromb Haemost 1995; 74: 1032-34.
- 7 Iacoviello L, Burzutta E, Di Castelnuovo A. et al. The 4G/5G polymorphism of the PAI – 1 promoter gene and the risk of myocardial infarction: a meta-analysis. Thromb Haemast 1998; 80: 1029-30.
- 8 Sartori MT, Wiman B, Vettore S. et al. 4G/5G polymorphism of PAI-1 gene promoter and fibrinolytic capacity in patients with deep vein thrombosis. Thromb Haemost 1998; 80: 956-60.
- 9 Stegnar M, Uhrin P, Peternel P. et al. The 4G/5G sequence polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene: relationship to PAI-1 level in venous thromboembolism. Thromb Haemost 1998; 79: 975-79.
- 10 Ridker MP, Hennekens CH, Lindpaintner K. et al. Arterial and venous thrombosis is not associated with the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor gene in a large cohorte of US men. Circulation 1997; 95: 59-62.
- 11 Iglesias Varela ML, Adamczuk YP. et al. Major and potential prothrombotic genotype in a cohort of patients with venous thromboembolism. Thromb Res 2001; 104: 317-24.
- 12 Akar N, Yilmaz E, Akar E. et al. Effect of plasminogen activator inhibitor –1 4G/5G polymorphism in Turkish deep vein thrombotic patients with and without FV 1691 G-A. Thromb Res 2000; 97: 227-30.
- 13 Visanji JM, Seargent J, Tahri D. et al. Influence of the –675 4G/5G dimorphism of the plasminogen activator inhibitor 1 promoter on thrombotic risk in patients with factor V Leiden. Br J Haematol 2000; 110: 135-38.
- 14 Zoller B, Garcia de Frutos P, Dahlback B. A common 4G allele in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene as a risk factor for pulmonary embolism and arterial thrombosis in hereditary protein S deficiency. Thromb Haemost 1998; 79: 802-7.
- 15 Martinelli I. Risk factor in venous thromboembolism. Thromb Haemost 2001; 86: 395-403.
- 16 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 venous thrombosis. Blood 1996; 88: 3698-703.
- 17 Falk G, Almqvist A, Nordenhem A. et al. Allele specific PCR for detection of a sequence polymorphism in the promoter region of the plasminogen activator inhibitor-1 (PAI -1) gene. Fibrinolysis 1995; 9: 170-74.
- 18 Segui R, Estelles A, Mira Y. et al. PAI-1 promoter 4G/5G genotype as an additional risk factor for venous thrombosis in subjects with genetic thrombophilic defects. Br J Haematol 2000; 111: 122-8.