RSS-Feed abonnieren
DOI: 10.1160/TH07-02-0103
A two adenine insertion polymorphism in the 3’ untranslated region of factor VII gene is associated with peripheral arterial disease but not with venous thrombosis
Results of case-control studiesPublikationsverlauf
Received
09. Februar 2007
Accepted after resubmission
20. Juli 2007
Publikationsdatum:
01. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200704/lookinside/thumbnails/10-1160-th07-02-0103-1.jpg)
Summary
Polymorphic variants of genes encoding blood coagulation proteins have been extensively studied as risk factors for venous or arterial thrombosis A variation in the 3' untranslated region (UTR) involved in the post-transcriptional regulation of factor VII (FVII) gene has been recently identified, a two adenine insertion/deletion at nucleotide 11293. In this study, we investigated its effect on the risk of thrombosis in the frame of two case-control studies, including patients suffering from peripheral arterial disease (PAD) or venous thromboembolic (VTE) disease. The 3’UTR FVII gene polymorphism was investigated i) in 181 patients who had symptomatic atherosclerotic disease of the lower limbs, ii) in 178 patients who had had at least one episode of objectively diagnosed deep venous thrombosis and iii) in controls matched for age and sex. Plasma FVII antigen (FVII:Ag) levels were lower in the presence of the 3’UTR 2A insertion (68.4 ± 12.3%, 81.3 ± 14.5% and 89.5 ± 13.7% in 2A/2A, 2A/0 and 0/0 subjects respectively, p<0.0001). No significant relationship was found with VTE disease. In the contrary we observed a lower risk of PAD for the 2A/2A compared to the 0/0 genotype after adjustment for traditional risk factors (hypercholesterolemia, smoking status, diabetes and hypertension), with an OR of 0.24 [95% CI 0.06–0.99]. In conclusion, the 2 adenine insertion in the 3’UTR of FVII gene, related to lower plasma FVII levels, is a genetic variation that may contribute to reduce the risk of PAD.
-
References
- 1 Bernardi F, Marchetti G, Pinotti M. et al. Factor VII gene polymorphisms contribute about one third of the factor VII level variation in plasma. Arterioscl Thromb Vasc Biol 1996; 16: 72-76.
- 2 Folsom AR. Hemostatic risk factors for atherothrombotic disease: an epidemiologic view. Thromb Haemost 2001; 86: 366-373.
- 3 Simmonds RE, Hermida J, Rezende SM. et al. Haemostatic genetic risk factors in arterial thrombosis. Thromb Haemost 2001; 86: 374-385.
- 4 Martinelli I. Risk factors in venous thromboembolism. Thromb Haemost 2001; 86: 395-403.
- 5 Peyvandi F, Garagiola I, Palla R. et al. Role of the 2 adenine (g.11293_11294 insAA) insertion polymorphisms in the 3’ untranslated region of the factor VII (FVII), gene: molecular characterization of a patient with severe deficiency. Hum Mutat 2005; 26: 455-461.
- 6 Alhenc-Gelas Arnaud E, Nicaud V. et al. Venous thromboembolic disease and the prothrombin, methylene tetrahydrofolate reductase and factor V genes. Thromb Haemost 1999; 81: 506-510.
- 7 Fontana P, Gaussem P, Aiach M. et al. P2Y12 haplotype is associated with peripheral arterial disease: a case-control study. Circulation 2003; 108: 2971-2973.
- 8 Reny JL, Alhenc-Gelas M, Fontana P. et al. The factor II G20210A gene polymorphism, but not factor V Arg506Gln, is associated with peripheral arterial disease: results of a case-control study. J Thromb Haemost. 2004; 2: 1334-1340.
- 9 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
- 10 O’Hara PJ, Grant FJ, Haldeman BA. et al. Nucleotide sequence of the gene coding for human factor VII, a vitamin K-dependent protein participating in blood coagulation. Proc Natl Acad Sci USA 1987; 84: 5158-5162.
- 11 Grzybowska EA, Wilczynska A, Siedlecki A. Regulatory functions of 3’UTRs. Biochem Biophys Res Com 2001; 288: 291-295.
- 12 Koster T, Rosendaal FR, Reitsma PH. et al. Factor VII and fibrinogen levels as risk factors for venous thrombosis. A case-control study of plasma levels and DNA polymorphisms-the Leiden Thrombophilia Study (LETS). Thromb Haemost 1994; 71: 719-722.
- 13 Austin H, Hooper WC, Lally C. et al. Venous thrombosis in relation to fibrinogen and factor VII genes among African-Americans. J Clin Epidemiol 2000; 53: 997-1001.
- 14 Lee AJ, Fowkes FG, Lowe GD. et al. Fibrinogen, factor VII and PAI-1 genotypes and the risk of coronary and peripheral atherosclerosis: Edinburgh Artery Study. Thromb Haemost 1999; 81: 553-560.
- 15 Meade TW, Ruddock V, Stirling Y. et al. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342: 1076-1079.
- 16 Carew JA, Basso F, Miller GJ. et al. A functional haplotype in the 5’ flanking region of the factor VII gene is associated with an increased risk of coronary heart disease. J Thromb Haemost 2003; 1: 2179-2185.
- 17 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.
- 18 Yamada Y, Matsuo H, Segawa T. et al. Assessment of genetic risk for myocardial infarction. Thromb Haemost 2006; 96: 220-227.
- 19 Wu AH, Tsongalis GJ. Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular diseases. Am J Cardiol 2001; 87: 1361-1366.
- 20 Ye Z, Liu EHC, Higgins JPT. et al. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66155 cases and 91307 controls. Lancet 2006; 367: 651-667.