Prothrombin Gene Mutation (Hereditary Thrombotic Predisposition)
Deep vein thrombosis (DVT) is a common disease, with an annual
incidence in the general population of approximately 1 per 1000. Risk
factors include both hereditary and acquired conditions.
Hyperactive coagulation pathways, hypoactive anticoagulant
mechanisms, or hypoactive fibrinolysis play an important role in the
predisposition to venous thrombosis.
Prothrombin is the precursor of the serine protease thrombin, a key
enzyme in the process of hemostasis and thrombosis.
One genetic variation, the 3'-untranslated region (3'UT) of the
prothrombin gene, G to A substitution at nucleotide position 20210, is
associated with venous thrombosis.
Carriers of the 20210A allele have a 2.8 fold increased risk of venous
thrombosis.
Therefore in addition to Factor V Leiden mutation, the MTHFR
mutation, and PAI-1 gene polymorphism, the prothrombin gene
mutation should be examined to assess the risk of thrombosis.
Refeneces:
1. Poort, S.R., F.R. Rosendaal, P.H.Reitsma and R.M.Bertina (1996) 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 88:3698-3703
2. Poort, S.R, J.J. Michiels, P.H.Reitsma, and RM.Bertina (1994) Homozygosity for
a novel missense mutation in the prothrombin gene causing a severe bleeding
disorder. Thromb. Haemost. 72: 819.
3. Degen, S.J.F. and E.W. Davies. (1987) Nucleotide sequence of the gene for
human prothrombin. Biochemistry 26:6165.
4. Glueck, C.J. M.J. Kupferminc, R.N. Fontaine, P. Wang, B.B. Weksler and A.
Eldor. (2001) Genetic hypofibrinolysis in complicated pregnancies. Obstet. and
Gynecol. 97:44-8.
5. Glueck, C.J., P. Wang, R.N. Fontaine, L. Sieve-Smith and J.E. Lang (2001)
Interaction of estrogen replacement therapy with the thrombophilic 20210 G/A
prothrombin gene mutation for atherothrombotic vascular disease: A
cross-sectional study of 275 hyperlipidemic women. Metabolism, 50:360-5.
For more information go to National Center for Biotechnology Information (NCBI).
Most abstracts and many full length articles can be printed from this web site.
www.ncbi.nlm.nih.gov/
|
