[en] The presence of the 2021 OA allele of the prothrombin
gene has recently been shown to be a risk factor of venous
thromboembolism, probably mediated through increased
prothrombin levels. The aim of the study was to determine
the frequency of the prothrombin 2021 OA allele in 193
consecutive unselected patients with venous thromboembolism
and 100 healthy controls and to analyze the clinical
profile associa!ed wi~h this new inherited thrombophilic
factof. In agreement with previous reports, we found a
frequency of 7.3% of heterozygous carriers of the 2021 OA
allele among patients and 1% among controls. We confirm
that plasma prothrombin levels are more elevated in
the individuals bearing the prothrombin 20210A allele
compared with those who do not. We did not find any relationship
between the presence of the prothrombin
2021 OA allele and either a family history of thromboembolism,
the rate of recurrences or the age at disease onset.
However, the co-inheritance in the same individual of both
prothrombin 2021 OA allele and factor V Leiden was associated
with a significantly lower age at disease onset suggesting
a synergistic contribution of both abnormalities.
Disciplines :
Hematology
Author, co-author :
Hainaut, Philippe
Gala, Jean-Luc
Lesage, Véronique
Lavenne, Edith
Azerad, Marie-Agnès ; Université Catholique de Louvain UCL St Luc > Département de médecine interne > Unité d'hemostase clinique
Zech, Francis
Heusterspreute, Michel
Philippe, Marianne
Moriau, Maurice
Language :
English
Title :
The prothrombin gene G20210A variant in an unselected thromboembolic population. A Belgian prospective clinical study
Dahlbäck B, CarIsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognised mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci. 1993; 90: 1004-8.
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.
Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet. 1993; 342: 1503-6.
Hainaut P, Azerad MA, Lehmann F et al. Prevalence of activated protein C resistance and analysis of clinical profile in thromboembolic patients. A Belgian prospective study. J Intern Med. 1997; 241: 427-33.
Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3'-untranslated region of the prothrombin gene is asssociated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996; 88: 3698-3703.
Friezner Degen SJ, Davie EW. Nucleotide sequence of the gene for human prothrombin. Biochemistry. 1987; 26: 6165-77.
Cumming AM, Keeney S, Salden A, Bhavnani M, Shwe KH, Hay CRM. The prothrombin gene G20210A variant: prevalence in a U.K. anticoagulant clinic population. Br Haematol. 1997; 98: 353-5.
Hillarp A, Zöller B, Svensson PJ, Dahlbäck. The 20210 A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep venous thrombosis. Thromb Haemost. 1997; 78: 990-2.
Alhenc-Gelas M, Le Cam-Duchez V, Emmerich J et al. The A20210 allele of the prothrombin gene is not frequently associated with the factor V Arg 506 to Gln mutation in thrombophilic families. Blood. 1997; 90: 1711.
Simioni P, Prandoni P, Lensing A et al. The risk of recurrent venous thromboembolism in patients with an Arg506-to-Gln mutation in the gene for Factor V (Factor V Leiden). N Engl J Med. 1997; 336: 399-403.
Rosendaal FR, Vos HL, Poort SL, Bertina RM. Prothrombin 20210A variant and age at thrombosis. Thromb Haemost. 1998; 79: 444.
Makris M, Preston FE, Beauchamp NJ et al. Co-inheritance of the 20210A allele of the prothrombin gene increases the risk of thrombosis in subjects with familial thrombophilia. Thromb Haemost. 1997; 78: 1426-9.
Zöller B, Holm J, Svensson PJ, Dahlbäck B. Elevated levels of prothrombin activation fragment 1+2 in plasma from patients with inherited APC-resistance and/ or protein S deficiency. Thromb Haemost. 1996; 75: 270-4.
Arruda VR, Annichino-Bizzacchi JM, Gonçalves MS, Costa FF. Prevalence of the prothrombin gene variant (nt20210A) in venous thrombosis and arterial disease. Thromb Haemost. 1997; 78: 1430-3.
Rosendaäl FR, Siscovick DS, Schwartz SM, Psaty BM, Raghunathan TE, Vos HL. A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood. 1997;90: 1747-50.
