From: Elizabeth M. Van Cott, M.D., and Michael Laposata, M.D., Ph.D., “Coagulation.” In: Jacobs DS et al, ed. The Laboratory Test Handbook, 5th Edition. Lexi-Comp, Cleveland, 2001; 327-358.
Related Information
Abstract This mutation is a common hereditary predisposition to venous thrombosis. DNA-based methods, such as the polymerase chain reaction (PCR)-based assay, are used to determine the presence of a specific mutation at nucleotide position 20210 in the prothrombin gene.
Specimen Whole blood
Container Varies with laboratory
Collection Routine venipuncture
Storage Instructions Do not centrifuge or freeze specimen. Store at 4degrees C or room temperature.
Turnaround Time Several days or longer (depending on how often test batches are performed)
Reference Interval Normal: prothrombin G20210A mutation not present
Use The test identifies individuals who have the prothrombin G20210A mutation. The results indicate whether an affected individual is heterozygous or homozygous for the mutation. The heterozygous form of the mutation is present in 2.3% of the general population and 6.2% of patients with venous thrombosis.1 It is present in 18% of cases of familial venous thrombosis.2
Methodology Commonly, polymerase chain reaction (PCR). The prothrombin G20210A mutation is a point mutation in which the guanine at nucleotide position 20210 is replaced by an adenine. The nucleotide change also allows the introduction of a new Hind III restriction site during PCR.2 To perform the test, DNA is isolated from whole blood and the mutation site is amplified by PCR. The PCR product is digested with Hind III and then subjected to agarose gel electrophoresis to separate the DNA bands based on size. The presence of a Hind III site at position 20210 can be determined by the pattern of DNA bands detected on the gel. The presence of a Hind III site at position 20210 indicates the presence of the prothrombin G20210A mutation. Heterozygotes and homozygotes can be specifically identified.
Additional Information The mutation involves a guanine to adenine transition at nucleotide position 20210 in an untranslated region of the gene. It is associated with elevated prothrombin levels and an increased risk for venous thrombosis.2,3,4 Individuals heterozygous for the prothrombin G20210A mutation have a two- to threefold increased risk for venous thrombosis.1 Homozygous individuals likely have an even higher risk for venous thrombosis. The risk for venous thrombosis is further increased in the presence of a second risk factor.5,6 Some studies have shown an increased risk for arterial thrombosis7 while other studies have not.8 It is possible that an increased risk for arterial thrombosis exists only when additional risk factors for arterial thrombosis are also present.9
Footnotes
1. van der Meer FJ, Koster T, Vandenbroucke JP, et al, “The Leiden Thrombophilia Study (LETS),”Thromb Haemost, 1997, 78(5):631-5.
2. 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 in Venous Thrombosis,”Blood, 1996, 88(10):3698-703.
3. Soria JM, Almasy L, Souto JC, et al, “Linkage Analysis Demonstrates That the Prothrombin G20210A Mutation Jointly Influences Plasma Prothrombin Levels and Risk of Thrombosis,”Blood, 2000, 95(9):2780-5.
4. Cattaneo M, Chantarangkul V, Taioli E, et al, “The G20210A Mutation of the Prothrombin Gene in Patients With Previous First Episodes of Deep-Vein Thrombosis: Prevalence and Association With Factor V G1691A, Methylenetetrahydrofolate Reductase C677T and Plasma Prothrombin Levels,”Thromb Res, 1999; 93(1):1-8
5. Martinelli I, Taioli E, Bucciarelli P, et al, “Interaction Between the G20210A Mutation of the Prothrombin Gene and Oral Contraceptive Use in Deep Vein Thrombosis,”Arterioscler Thromb Vasc Biol, 1999, 19(3):700-3.
6. Martinelli I, Sacchi E, Landi G, et al, “High Risk of Cerebral-Vein Thrombosis in Carriers of a Prothrombin Gene Mutation and in Users of Oral Contraceptives,”N Engl J Med, 1998, 338(25):1793-7.
7. Franco RF, Trip MD, ten Cate H, et al, “The 20210 G/A Mutation in the 3′-Untranslated Region of the Prothrombin Gene and the Risk for Arterial Thrombotic Disease,”Br J Haematol, 1999, 104(1):50-4.
8. Ridker PM, Hennekens CH, and Miletich JP, “G20210A Mutation in Prothrombin Gene and Risk of Myocardial Infarction, Stroke, and Venous Thrombosis in a Large Cohort of U.S. Men,”Circulation, 1999, 99(8):999-1004.
9. Inbal A, Freimark D, Modan B, et al, “Synergistic Effects of Prothrombotic Polymorphisms and Atherogenic Factors on the Risk of Myocardial Infarction in Young Males,”Blood, 1999, 93(7):2186-90.
References
De Stefano V, Chiusolo P, Paciaroni K, et al, “Prothrombin G20210A Mutant Genotype Is a Risk Factor for Cerebrovascular Ischemic Disease in Young Patients,”Blood, 1998, 91(10) :3562-3565.
Eikelboom JW, Baker RI, Parsons R, et al, “No Association Between the 20210 G/A Prothrombin Gene Mutation and Premature Coronary Artery Disease,”Thromb Haemost, 1998, 80(6):878-880.
