Polymorphism of beta(2)-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 bind ing domain of beta(2)-glycoprotein I (beta(2)GPI) in patients,vith systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS), and to a nalyze the clinical correlations of such mutations with thromboembolic comp lications. Methods. Exons 7 and 8 of beta(2)GPI, which encode for its fifth domain, we re amplified by polymerase chain reaction, and the presence of mutations wa s determined by restriction digestion and single-strand conformation polymo rphism analysis. A clinical correlation with these mutations and the presen ce of antiphospholipid antibodies (aPL), lupus anticoagulant (LAC), anti-be ta(2)GPI 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 hete rozygous 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-beta(2)GPI antibodies was found. In pati ents 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 beta(2)GPI i n these patients with SLE and/or APS were similar to those previously repor ted 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.