Molecular analysis of prothrombotic gene variants in venous thrombotic diseases. Different risk factors in different sex and clinical forms.

Abstract

Background The role of prothrombotic gene variants as risk factors for venous thrombotic diseases is controversial and the ordering of tests for thrombophilia in the clinical context is scarcerly respective of evidence-based data. Methods We studied FVL, FVR2, FII G20210A, MTHFR C677T and A1298C, beta-fibrinogen -455 G>A, FXIII V34L, HPA-1 L33P variants and PAI-1 4G/5G alleles in: 343 patients with deep vein thrombosis (DVT), 164 with pulmonary embolism (PE), 126 with superficial vein thrombosis (SVT), 118 with portal vein thrombosis (PVT), 75 with cerebral vein thrombosis (CVT), 119 with retinal vein thrombosis (RVT) in comparison with 430 subjects from the general population (GP) of the same geographical area (Southern Italy). Results About 40% of patients with DVT, PE and SVT have a prothrombotic predisposition represented by FVL, FVR2 and FII G20210A variants (significantly more frequent than in the general population), significantly higher in PE males. While, in patients with PVT and CVT only FII G20210A variant is more frequent particularly in females. Finally, RVT is poorly related to prothrombotic risk factors, confirming that local vascular and other factors have a pivotal role in its pathogenesis. Conclusions Our data indicate that only FVL, FVR2 and FII G20210A are related to vein thrombotic diseases while all the other gene variants, frequently ordered in the clinical context, do not have a role as risk factors. Furthermore, the evidence of a sex difference for some variants, once confirmed in larger populations, may help to promote sex-specific prevention of such diseases.