Thromb Haemost 1999; 81(06): 861-864
DOI: 10.1055/s-0037-1614588
Letters to the Editor
Schattauer GmbH

The Prothrombin 20210A Allele and Its Association with Myocardial Infarction

S. A. Croft
1   From the Division of Molecular and Genetic Medicine, University of Sheffield, Royal Hallamshire Hospital, Sheffield, U.K.
,
M. E. Daly
1   From the Division of Molecular and Genetic Medicine, University of Sheffield, Royal Hallamshire Hospital, Sheffield, U.K.
,
R. P. Steeds
2   Department of Cardiology, Royal Hallamshire Hospital, Sheffield, U.K.
,
K. S. Channer
2   Department of Cardiology, Royal Hallamshire Hospital, Sheffield, U.K.
,
N. J. Samani
3   Department of Cardiology, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester, U.K.
,
K. K. Hampton
1   From the Division of Molecular and Genetic Medicine, University of Sheffield, Royal Hallamshire Hospital, Sheffield, U.K.
› Author Affiliations
Further Information

Publication History

Received 16 November 1998

Accepted after resubmission 24 February 1999

Publication Date:
09 December 2017 (online)

Summary

The relationship between the prothrombin (PT) 20210A allele and arterial disease is controversial. We conducted a case-control study to assess its contribution to risk of myocardial infarction (MI). Five hundred and thirty-nine acute MI patients and 498 control subjects aged <75 years were studied. Two percent of cases carried the PT20210A allele compared to 2.8% of controls. The odds ratio for MI was 0.72 (95% CI 0.32-1.60) indicating that the PT20210A allele confers no increased risk for MI. Subgroup analysis showed no association between the PT20210A allele and either premature MI or MI in females. We conclude the PT20210A allele is not a risk factor for MI and suggest that discrepancies in studies relating the PT20210A allele to MI may be due to difficulties in estimating its low allelic frequency in the general population and thus random differences in the observed frequencies in the control populations studied.

 
  • References

  • 1 Jackson CM. Physiology and biochemistry of prothrombin. In. Haemostasis and Thrombosis Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. (eds) Edinburgh, UK: Churchill Livingstone; 1994: 397-438.
  • 2 Dahlbäck B. Inherited Thrombophilia. Resistance to activated protein C as a pathogenic factor of venous thromboembolism. Blood 1995; 85: 607-14.
  • 3 Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V, Chandy M, Dahlbäck B, Ginter EK, Miletich JP, Rosendaal FR, Seligsohn U. Inherited Thrombophilia: Part 1. Thromb Haemost 1996; 76: 651-62.
  • 4 Kalafatis M, Bertina RM, Rand MD, Mann KG. Characterization of the molecular defect in factor V R506Q. J Biol Chem 1995; 270: 4053-7.
  • 5 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 1996; 88: 3698-703.
  • 6 Hillarp A, Zöller B, Svensson PJ, Dahlbäck B. 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.
  • 7 Brown K, Luddington R, Williamson D, Baker P, Baglin T. Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 3’-untranslated region of the prothrombin gene. Brit J Haematol 1997; 98: 907-9.
  • 8 Leroyer C, Mercier B, Oger E, Chenu E, Abgrall J-F, Férec C, Mottier D. Prevalence of 20210 A allele of the prothrombin gene in venous thromboembolism patients. Thromb Haemost 1998; 80: 49-51.
  • 9 Makris M, Preston FE, Beauchamp NJ, Cooper PC, Daly ME, Hampton KK, Bayliss P, Peake IR, Miller GJ. 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.
  • 10 Rosendaal 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.
  • 11 Doggen CJM, Manger Cats V, Bertina RM, Rosendaal FR. Interaction of coagulation defects and cardiovascular risk factors. Increased risk of myocardial infarction associated with factor V Leiden or prothrombin 20210A. Circulation 1998; 97: 1037-41.
  • 12 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.
  • 13 Arruda VR, Siquiera LH, Chiaparini LC, Coelho OR, Mansur AP, Ramires A, Annichino-Bizzacchi JM. Prevalence of the prothrombin gene variant 20210 G→A among patients with myocardial infarction. Cardiovasc Res 1998; 37: 42-5.
  • 14 Ferraresi P, Marchetti G, Legnani C, Cavallari E, Castoldi E, Mascoli F, Ardissino D, Palareti G, Bernardi F. The heterozygous 20210 G/A prothrombin genotype is associated with early venous thrombosis in inherited thrombophilias and is not increased in frequency in artery disease. Arterioscler Thromb Vasc Biol 1997; 17: 2418-22.
  • 15 WHO (Report of the joint International Society and Federation of Cardiology/World Health Organisation Task Force on standardization of clinical nomenclature) Nomenclature and criteria for diagnosis of ischaemic heart disease. Circulation 1979; 59:: 607-9.
  • 16 Beauchamp NJ, Daly ME, Makris M, Preston FE, Peake IR. A novel mutation in intron K of the PROS1 gene causes aberrant RNA splicing and is a common cause of protein S deficiency in a UK thrombophilia cohort. Thromb Haemost 1998; 79: 1086-91.
  • 17 Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet 1955; 19: 251.
  • 18 Steeds R, Adams M, Smith P, Channer K, Samani NJ. Distribution of tissue plasminogen activator insertion/deletion polymorphism in myocardial infarction and control subjects. Thromb Haemost 1998; 79: 980-4.
  • 19 Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V, Chandy M, Dahlbäck B, Ginter EK, Miletich JP, Rosendaal FR, Seligsohn U. Inherited Thrombophilia: Part 2. Thromb Haemost 1996; 76: 824-34.
  • 20 Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke and venous thrombosis in apparently healthy men. N Engl J Med 1995; 332: 912-7.
  • 21 Rosendaal FR, Siscovick DS, Schwartz SM, Beverly RK, Psaty BM, Long-streth Jr WT, Raghunathan TE, Koepsell TD, Reitsma PH. Factor V Leiden (Resistance to activated protein C) increases the risk of myocardial infarction in young women. Blood 1997; 89: 2817-21.
  • 22 Corral J, Gonzalez-Conejero R, Lozano ML, Rivera J, Heras I, Vicente V. The venous thrombosis risk factor 20210A allele of the prothrombin gene is not a major risk factor for arterial thrombotic disease. Brit J Haematol 1997; 99: 304-7.
  • 23 Kaduskar S, Bradshaw H, Rayner M.. Coronary heart disease statistics, 1997 Edition. British Heart Foundation Statistics Database
  • 24 Fearon WF, Cooke JP. Acute myocardial infarction in a young woman with systemic lupus erythematosus. Vasc Med 1996; 1: 19-23.
  • 25 Franco RF, Trip MD, ten Cate H, Prins MH, Kastelein JJP, Zago MA, Reitsma PH. Analysis of the 20210 G→A prothrombin and factor V Leiden mutations in patients with premature arterial vascular disease. Blood 1997; 90: 1126 (abstr, suppl)
  • 26 Rosendaal FR, Doggen CJM, Zivelin A, Arruda VR, Aiach M, Siscovick DS, Hillarp A, Watzke HH, Bernardi F, Cumming AM, Preston FE, Reitsma PH. Geographic distribution of the 20210 G to A Prothrombin variant. Thromb Haemost 1998; 79: 706-8.