G20210A prothrombin gene variant and clinical outcome in patients with a first acute coronary syndrome.

BACKGROUND AND OBJECTIVES The prognostic value of the G20210A prothrombin gene polymorphism in patients with a first acute coronary syndrome has not been previously assessed. We conducted a prospective study to investigate this issue. DESIGN AND METHODS Genotyping at the 20210 prothrombin gene locus was performed in 162 patients with a first episode of myocardial infarction (MI) or unstable angina (UA) occurring before 65 years of age. Patients were stratified according to cardiovascular risk factors and to treatment strategy. The subsequent two-year relative risk (RR) of adverse events (death, MI and UA) was adjusted for possible confounders and analyzed according to genotype, risk factor category, and treatment allocation. RESULTS In the entire study population, the prothrombin variant did not significantly increase the two-year risk of events: the adjusted RR for GA vs GG carriers was 1.82 (95% CI 0.68-4.89). However, in the absence of traditional cardiovascular risk factors the risk of events was consistently higher: among the 46 patients without hypertension, diabetes and hypercholesterolemia, GA vs GG carriership was associated with an adjusted RR at two years of 5.64 (95% CI 1.07-29.84). The gene variant also enhanced the risk of events among the 98 patients who did not undergo myocardial revascularization procedures (RR for GA vs GG: 2.89, 95% CI 1.04-8.00), but not among those who did. INTERPRETATION AND CONCLUSIONS The present prospective study suggests that heterozygosity for the G20210A prothrombin polymorphism adversely affects prognosis after a first acute coronary syndrome in the subgroup of patients without metabolic risk factors and in those not treated by revascularization procedures.

[1]  P. Serruys,et al.  Three-Year Outcome After Coronary Stenting Versus Bypass Surgery for the Treatment of Multivessel Disease , 2004, Circulation.

[2]  F. Burzotta,et al.  G20210A Prothrombin gene polymorphism and coronary ischaemic syndromes: a phenotype-specific meta-analysis of 12 034 subjects , 2003, Heart.

[3]  R. Becker,et al.  Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. , 2003, American heart journal.

[4]  C. Butt,et al.  Combined carrier status of prothrombin 20210A and factor XIII-A Leu34 alleles as a strong risk factor for myocardial infarction: evidence of a gene-gene interaction. , 2003, Blood.

[5]  A. M. Leone,et al.  Increased prevalence of the G20210A prothrombin gene variant in acute coronary syndromes without metabolic or acquired risk factors or with limited extent of disease. , 2002, European heart journal.

[6]  R. Peters,et al.  Genetic Variation in Coagulation and Fibrinolytic Proteins and Their Relation With Acute Myocardial Infarction: A Systematic Review , 2001, Circulation.

[7]  H. White,et al.  Prevalence of Factor V Leiden and Prothrombin Variant G20210A in Patients Age ,50 Years With No Significant Stenoses at Angiography Three to Four Weeks After Myocardial Infarction , 2016 .

[8]  F. Burzotta,et al.  G20210A prothrombin gene polymorphism and extent of coronary disease. , 2000, Thrombosis and haemostasis.

[9]  L. Wallentin,et al.  Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial , 2000, The Lancet.

[10]  F F Costa,et al.  Prevalence of the Prothrombin Gene Variant (nt20210A) in Venous Thrombosis and Arterial Disease , 1997, Thrombosis and Haemostasis.

[11]  P. Reitsma,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. , 1996, Blood.

[12]  E. Braunwald,et al.  Unstable angina. A classification. , 1989, Circulation.

[13]  S Böthig,et al.  WHO MONICA Project: objectives and design. , 1989, International journal of epidemiology.