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Combined Effect of Hemostatic Gene Polymorphisms and the Risk of Myocardial Infarction in Patients with Advanced Coronary Atherosclerosis

2008; Public Library of Science; Volume: 3; Issue: 2 Linguagem: Inglês

10.1371/journal.pone.0001523

1932-6203

Nicola Martinelli, Elisabetta Trabetti, Mirko Pinotti, Oliviero Olivieri, Marco Sandri, Simonetta Friso, Francesca Pizzolo, Claudia Bozzini, Pier Paolo Caruso, Ugo Cavallari, Suzanne Cheng, Pier Franco Pignatti, Francesco Bernardi, Roberto Corrocher, Domenico Girelli,

Coagulation, Bradykinin, Polyphosphates, and Angioedema

Relative little attention has been devoted until now to the combined effects of gene polymorphisms of the hemostatic pathway as risk factors for Myocardial Infarction (MI), the main thrombotic complication of Coronary Artery Disease (CAD). The aim of this study was to evaluate the combined effect of ten common prothrombotic polymorphisms as a determinant of MI.We studied a total of 804 subjects, 489 of whom with angiographically proven severe CAD, with or without MI (n = 307; n = 182; respectively). An additive model considering ten common polymorphisms [Prothrombin 20210G>A, PAI-1 4G/5G, Fibrinogen beta -455G>A, FV Leiden and "R2", FVII -402G>A and -323 del/ins, Platelet ADP Receptor P2Y12 -744T>C, Platelet Glycoproteins Ia (873G>A), and IIIa (1565T>C)] was tested. The prevalence of MI increased linearly with an increasing number of unfavorable alleles (chi(2) for trend = 10.68; P = 0.001). In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors. As compared to subjects with 3-7 alleles, those with few (</=2) alleles had a decreased MI risk (OR 0.34, 95%CIs 0.13-0.93), while those with more (>/=8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03-6.01). The number of procoagulant alleles correlated directly (r = 0.49, P = 0.006) with endogenous thrombin potential.The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD.