Correlation between β2-glycoprotein I valine/leucine247 polymorphism and anti-β2-glycoprotein I antibodies in patients with primary antiphospholipid syndrome

Objectives. beta 2-Glycoprotein I (beta 2GPI) exon 7 polymorphism leads to a valine-leucine amino acid exchange at position 247 in domain 5 of beta 2GPI, between the phospholipid binding site and the cryptic site of the epitopes for anti-beta 2CPI antibodies. Therefore, position 247 polymorphism may affect the conformational change of beta 2GPI and the exposure of the epitopes for anticardiolipin antibodies (aCL) (= anti-beta 2GPI antibodies). In this study we analysed the genetic polymorphism of beta 2GPI in a British cohort of well-defined antiphospholipid syndrome (APS) patients. Methods. This study comprised 88 Caucasoid patients with APS [57 with primary APS and 31 with APS secondary to systemic lupus erythematosus (SLE)]. Polymorphism assignment was determined by polymerase chain reaction followed by allele-specific restriction enzyme digestion (PCR-RFLP). The presence of anti-beta 2GPI antibodies was detected by ELISA utilizing irradiated ELISA plates. Results and conclusions. Anti-beta 2CPI antibodies were present in 28 of 57 primary APS patients (49%) and in 19 of 31 secondary APS patients (61%). The allele containing valine(247) was significantly more frequent in primary APS patients with anti-beta 2GPT antibodies than in controls (OR = 2.51, 95% CI 1.03-6.13, P = 0.0396) or in primary APS patients without anti-beta 2GPI antibodies (OR = 2.92, 95% CI 1.16-7.39, Y = 0.0204). This tendency was not found in the secondary APS group. In conclusion, the beta 2GPT polymorphism, valine/leucine(247), is correlated with anti-beta 2GPI antibody production in patients with primary APS, and valine247 may be important in the formation of beta 2GPI antigenicity.