Polymorphism of β₂-glycoprotein I at codons 306 and 316 in patients with systemic lupus erythematosus and antiphospholipid syndrome

Objective. To determine the frequency of mutations in the phospholipid binding domain of β₂glycoprotein I (β₂GPI) in patients with systemic lupus erythematosus (SLE)and/or antiphospholipid syndrome (APS), and to analyze the clinical correlations of such mutations with thromboembolic complications. Methods. Exons 7 and 8 of β₂GPI, which encode for its fifth domain, were amplified by polymerase chain reaction, and the presence of mutations was determined by restriction digestion and single-strand conformation polymorphism analysis. A clinical correlation with these mutations and the presence of antiphospholipid antibodies (aPL), lupus anticoagulant (LAC), anti-β₂GPI antibody, and the development of thromboembolic complications was performed using chi-square and Fisher's exact tests. Results. From a total of 143 patients studied, we found that 5.6% were heterozygous for the mutation at exon 7 (codon 306), and 7.7% were heterozygous for the mutation at exon 8 (codon 316). No homozygous subjects were found for either mutation. No significant correlation between these mutations and the presence of aPL, LAC, or anti-β₂GPI antibodies was found. In patients with SLE (n = 95), 4 of 6 patients with exon 8 mutation had thrombosis, compared with 22 of 82 patients without the mutation (P = 0.043). Conclusion. The prevalence of mutations in the fifth domain of β₂GPI in these patients with SLE and/or APS were similar to those previously reported for the general population. Heterozygosity for either mutation does not influence the incidence of aPL, but in patients with SLE, the mutation at exon 8 may predispose to thrombosis as an independent factor.