Val/Leu247 and Trp/Ser316 polymorphisms in β2 glycoprotein I and their association with thrombosis in unselected Chilean patients

It is known that polymorphisms of β 2-glycoprotein I (β 2GPI) in exon 7 affect interaction between the phospholipid binding site and the antibodies, and that other polymorphisms in exon 8 increase the generation of antibodies. In this study, we analyzed genetic polymorphisms of β 2GPI in unselected Chilean patients to determine the prevalence of β 2GPI polymorphisms in the phospholipid domain in patients with venous and arterial thrombosis and the clinical correlation with thromboembolic complications. This study comprised 149 patients with venous and arterial thrombosis (62 with venous thrombosis and 87 with arterial thrombosis) and 160 healthy controls with no previous history of thrombosis. Polymorphisms of exons 7 and 8 of β 2GPI, which encode for its fifth domain, were determined by PCR-RFLP. The presence of aPL or anti-β 2GPI in the patients was detected by ELISA. Anti-β 2GPI were present in 8/149 patients (5.4%); of these, five had aCL antibodies of low titer. The allele containing Val/Leu247 and Trp/Ser316 was significantly more frequent in patients with thrombosis than in the control group (OR=3.1, CI 1.6–6.0, p=0.0003; OR=2.9, CI 1.1–8.6, p=0.027, respectively). These polymorphisms did not correlate with aPL or anti-β 2GPI but significant differences were observed with venous thrombosis (p=<0.0001) and arterial thrombosis (p=0.026). In conclusion, the β 2GPI polymorphisms Val/Leu247 and Trp/Ser316 are not related to the presence of anti-β 2GPI antibodies in unselected Chilean patients with venous and arterial thrombosis, but they are significantly associated with venous and arterial thrombosis.