The combination of thrombophilic genotypes is associated with definite antiphospholipid syndrome

Background and Objectives. Thrombosis and pregnancy morbidity are clinical features of the definite antiphospholipid syndrome (APS). These clinical co mplications are also associated with the presence of inherited thrombophili as. Interactions between acquired and genetic risk factors are becoming inc reasingly related to a higher thrombotic risk. The aim of our study was to determine the prevalence of four common gene polymorphisms in patients with antiphospholipid antibodies (aPL). Design and Methods. A series of 105 consecutive unselected patients with aP L grouped as having APS (n= 69) and not having APS (n= 36) was studied. A c ontrol group of 200 healthy subjects was also investigated for the presence of factor V Leiden (FVL), the 20210A allele of the prothrombin (PT-20210A) gene, the thermolabile variant (677TT) of methylenetetrahydrofolate reduct ase (MTHFR), and the 4G/4G genotype of the plasminogen activator inhibitor (PAI-1) promoter. Results. Two patients who belong to the APS group carried the FVL while PT- 20210A was found in 6 patients with APS (8.7%) and in 1 of the non-APS grou p (2.8%). The prevalence of FVL was similar to that found in the control gr oup whereas PT-20210A was significantly more frequent in APS patients than in normal controls (2.0%, rho =0.02). The MTHFR-677TT was found in 22.0%, 1 5.1% and 13.0%, and the PAI-1 (4G/4G) in 27.5%, 22.8% and 23.5% of APS, non -APS patients and normal controls, respectively, Furthermore, combinations of PT-20210A or FVL with PAI-1 (4G/4G) were significantly more frequent in APS patients (5.8%) than in normal controls (0.5%, p=0.016). This differenc e was not found between non-APS patients and normal subjects. Interpretation and Conclusions. Present data indicate that testing for heri table thrombophilia would be important to identify aPL subjects with an inc reased risk of developing APS. (C) 2001, Ferrata Storti Foundation.