Prothrombotic gene variants as risk factors of acute myocardial infarction in young women
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RESEARCH
Open Access
Prothrombotic gene variants as risk factors of acute myocardial infarction in young women Rossella Tomaiuolo1,2,3, Chiara Bellia4, Antonietta Caruso4, Rosanna Di Fiore2, Sandro Quaranta2, Davide Noto5, Angelo B Cefalù5, Pierpaolo Di Micco6, Federica Zarrilli7, Giuseppe Castaldo1,2*, Maurizio R Averna5* and Marcello Ciaccio4*
Abstract Background: Acute myocardial infarction (AMI) in young women represent an extreme phenotype associated with a higher mortality compared with similarly aged men. Prothrombotic gene variants could play a role as risk factors for AMI at young age. Methods: We studied Factor V Leiden, FII G20210A, MTHFR C677T and beta-fibrinogen -455G>A variants by real-time PCR in 955 young AMI (362 females) and in 698 AMI (245 females) patients. The data were compared to those obtained in 909 unrelated subjects (458 females) from the general population of the same geographical area (southern Italy). Results: In young AMI females, the allelic frequency of either FV Leiden and of FII G20210A was significantly higher versus the general population (O.R.: 3.67 for FV Leiden and O.R.: 3.84 for FII G20210A; pA
Female subjects
21/870 (2.4%)
22/870 (2.5%)
395/916 (43.1%)
108/744 (14.5%)
Male subjects
21/848 (2.5%)
21/848 (2.5%)
365/902 (40.5%)
78/564 (13.8%)
procoagulant effect. The most common prothrombotic variants are: Factor V (FV) Leiden, which causes resistance to protein C; prothrombin (FII) G20210A variant, that causes a higher plasma level of FII; the C677T variant of methylene-tetrahydrofolate reductase (MTHFR) enzyme which impairs the homocysteine pathway thereby causing higher serum levels of homocysteine that acts as a trigger for coagulation at endothelial level; and the -455G>A variant of beta-fibrinogen which causes increased levels of fibrinogen [5]. Prothrombotic gene variants are already known to be risk factors for recurrent venous thrombosis [6], particularly in patients with other predisposing disease [7] whereas there is no consensus regarding the role of such variants as risk factors for arterial disorders, including AMI and young AMI [8-12]. The discordant results reported so far may reflect heterogeneous selection criteria and the different number of AMI patients and controls analyzed in different studies [13], and the fact that most studies pooled male and female patients thereby obscuring eventual gender differences. The different results may also depend on the variable incidence of prothrombotic variants in subjects of different ethnic background, and on the fact that some studies compared the frequency of prothrombotic gene variants obtained in AMI patients with that of control populations of other geographical areas. The aim of the present study was to evaluate the potential role of the four prothrombotic gene variants as risk factors of either young AMI and AMI in female and male subjects in comparison to a large group of individuals from the general population of the same geographic area, whose sex and age distribution corresponded to the anagrap
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