Polymorphisms -455G/A and -148C/T and Fibrinogen Plasmatic Level as Risk Markers of Coronary Disease and Major Adverse Cardiovascular Events

Abstract

Some polymorphisms in genes codifying for fibrinogen have been correlated with plasma levels of this protein, and several studies reported their associations with acute cardiovascular events. In the present study, 118 subjects with unstable and stable coronary diseases were enrolled to determinate the associations among fibrinogen gene polymorphisms, plasma fibrinogen levels, and major cardiovascular adverse events in a sample of southwestern Mexico. The groups, including 81 control subjects, were matched for age, sex, body mass index, and sedentarism. Plasma fibrinogen levels and the polymorphisms 455G/A, -148C/T, +1689T/G, and Bcl I of the gene of fibrinogen were compared in all groups. Plasma fibrinogen levels (>465 mg/dl) were significant in patients with coronary disease. Fibrinogen plasma values>450 mg/dl were associated with cardiovascular mortality during the follow-up analysis of the unstable coronary disease group (p=0.04). The allelic loads of -455A and -148T were associated with plasma fibrinogen levels>450 mg/dl (p<0.003 and p=0.03, respectively) and with coronary disease (p=0.016 and p<0.006, respectively). The follow-up of posterior events after an acute coronary event showed that the genetic load of the -148T allele was associated with major adverse cardiovascular events (RR=1.8, 95%CI=1.01‐3.35, p=0.04). Fibrinogen plasmatic levels>450 mg/dl and the fibrinogen polymorphisms -455G/A and 148C/T had association with MACE and coronary disease. This study suggests that these gene polymorphisms are associated with cardiovascular risk.

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“…gen plays a major role in platelet aggregation via enzymatic conversion to fibrin and is also the main determinant of plasma viscosity and erythrocyte aggregation [13]. Several studies and meta-analyses have investigated the association between the fibrinogen level and cardiovascular diseases [14,15]. Fibrinogen was found to be an independent risk factor for cardiovascular disease in these studies.…”

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“…It was also shown that the allelic loads of -455 G/A and -148 C/T were associated with plasma fibrinogen concentrations >450 mg/dL ( p < 0.003 and p = 0.03) and with a risk of CAD ( p = 0.016 and p < 0.006). Moreover, the follow-up of posterior events after an acute coronary event showed that the genetic load of the -148 C/T allele was associated with major adverse cardiovascular events (RR = 1.8; 95% CI: 1.01–3.35, p = 0.04) [ 86 ]. A meta-analysis of 26 clinical trials, by Gu et al, also assessed the association between the -455 G/A polymorphism and the risk of ischemic stroke.…”

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“…Cardiovascular disease is a frequently occurring disease that seriously endangers human health. [19][20][21] Many cardiovascular diseases, such as hypertension, valvular disease, myocardial infarction, and congenital heart disease, can lead to cardiac hypertrophy and cause heart failure or even sudden death. [22][23][24][25] Therefore, myocardial hypertrophy has become one of the independent risk factors for cardiovascular disease morbidity and mortality around the world, and its pathogenesis and prevention and treatment have always been the focus of research in the field of cardiovascular diseases.…”