Factor II Mutation

Factor II Mutation

Prothrombin which is also called Factor II, is a protein  in the blood involved in the blood clotting mechanism. It is needed to form fibrin which is then required for blood clotting. Recently, a new polymorphism in the 3’-untranslated region of the Prothrombin gene (F2), guanine 20210 adenine mutation is described which alters the polyadenylation site of the gene resulting in excess mRNA synthesis with subsequent increased protein expression. That is found to be associated with elevated levels of prothrombin and results in increased risk for hypercoagulability disorders (Thrombophilia). [1], [2], [3]

The G20210A is the second more frequent variant implicated in hypercoagulability disorders of the caucasian population and has the prevelance of approximately 1 to 4% in the normal population.  İt is more prevalant in southern European and rarely seen in Asians or Africas.[4] A study of patients in Turkey revealed the presence of the prothrombin 20210a mutation in 0.7% of subjects.[5] The G20210A variant, an autosomal recessive deficiency, which is usually not accompanied by other factor mutations ( i.e. factor V-Leiden) may be inherited heterozygous (1 pair), or rarely, homozygous (2 pairs), and not mainly related to gender or blood type. Also with other risk factors; including congenital thrombophilia (deficiency of protein C and protein S...etc.), temporary factors such as surgery, immobility, pregnancy and chronic conditions such as obesity and cancer, homozygous mutations increase the risk of thrombosis more than heterozygous mutations.[6]

The diagnosis of a prothrombin mutation is made by a blood test that requires DNA analysis of F2, gene encoding prothrombin, to identify the common substitution, a G>A transition at nucleotide 20210A. Although simply applying a test of prothrombin concentrations in plasma may give an idea about  prothrombin mutation, it is the molecular test with satisfying and reliable results allowing to success genotypic identification. [7]

Annotated Bibliography

1- Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. 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. Nov 15 1996;88(10):3698-703

2-Pollak ES, Lam HS, Russell JE. The G20210A mutation does not affect the stability of prothrombin mRNA in vivo. Blood. Jul 1 2002;100(1):359-62

3-Ceelie H, Spaargaren-van Riel CC, Bertina RM, Vos HL. G20210A is a functional mutation in the prothrombin gene; effect on protein levels and 3'-end formation. J Thromb Haemost. Jan 2004;2(1):119-27

4-Rosendaal FR, Doggen CJ, Zivelin A, et al. Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost. Apr 1998;79(4):706-8

5-Irdem A, Devecioglu C, Batun S, Soker M, Sucakli IA. Prevalence of factor V Leiden and prothrombin G20210A gene mutation. Saudi Med J. Apr 2005;26(4):580-3.

6-DeStefano V, Martinelli I, Mannucci P, et al. The risk of recurrent deep venous thromboembolism among heterozygous carriers of the G20210A prothrombin gene mutation. Br J Hematol. 2001;113:630–635.

7-Varga EA, Moll S., Cardiology patient pages. Prothrombin 20210 mutation (factor II mutation). Circulation. 2004 Jul 20;110(3):e15-8.