To our knowledge, this is the first study investigating the possible involvement of the prothrombotic gene variants as risk factors of AMI in different gender and age subjects. Our data indicate that the FV Leiden and FII G20201A variants in females represent a risk factors for young AMI, namely, patients who developed the first episode of AMI before reach the age of 45 years. The FV Leiden is associated to a resistance to the inhibitory effect of protein C that enhances a procoagulant activity, while the FII G20210A variant causes higher levels and more pronounced procoagulant activity of FII, both of which may predispose to ischemic diseases . We observed a higher frequency of such variants only in young AMI females and not in young AMI males or in AMI females, confirming that young AMI females are a well-defined group of subjects with peculiar risk factors [1–3]. On the other hand, risk factors for young AMI are different from those observed in AMI, e.g., the atherosclerosis burden is less relevant in young AMI, particularly in women . While, genetic factors seem to be more relevant [4, 17, 18]. Our data are in accordance with the results of a large study by Mannucci et al.  in which there was a higher (albeit not significantly different) allelic frequency of the FII G20210A variant in young AMI than in controls; however the authors did not analyze the data in terms of gender, and the group they studied contained more men than women (1680 men and 210 female). In the same study, the FV Leiden mutation was significantly more frequent in young AMI patients.
Furthermore, our data indicate that the C677T MTHFR variant confers a higher risk for AMI to males. Such variant is a known risk factor for coronary heart disease , but our study revealed that only male homozygous subjects for this variant have a higher odds ratio for AMI. The MTHFR C677T variant causes higher homocysteine and lower folate levels in serum, and this is particularly true in homozygous subjects. In this context, it is noteworthy that the mechanism by which high levels of circulating homocysteine or low levels of folate may contribute to AMI pathogenesis it is still obscure . Interestingly, we observed a higher frequency of MTHFR C677T only in AMI males and not in young AMI patients. It is conceivable that this variant acts as a risk factor in older but not in young subjects because the latter have a better folate intake . The other three prothrombotic variants we investigated (FV Leiden, FII G20201A and -455 G>A in the gene encoding the beta-fibrinogen) do not seem to contribute to AMI risk. These data are in partial discordance with previous studies that implicated these gene variants in AMI, but in most cases the sample size and the differences between patients and controls were small. Another study, in agreement with ours, excluded a major role of these variants as risk factors for AMI  and a large meta-analysis concluded that prothrombotic gene variants are only moderately associated with the risk of coronary diseases .