title: Correlation between beta2-glycoprotein I valine/leucine247 polymorphism and anti-beta2-glycoprotein I antibodies in patients with primary antiphospholipid syndrome.
abstract: OBJECTIVE
  Beta2-Glycoprotein I (beta2GPI) exon 7 polymorphism leads to a valine leucine amino acid exchange at position 247 in domain 5 of beta2GPI, between the phospholipid binding site and the cryptic site of the epitopes for anti-beta2GPI antibodies. Therefore, position 247 polymorphism may affect the conformational change of beta2GPI and the exposure of the epitopes for anticardiolipin antibodies (aCL) (= anti-beta2GPI antibodies). In this study we analysed the genetic polymorphism of beta2GPI 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-beta2GPI antibodies was detected by ELISA utilizing irradiated ELISA plates.
  
  
  CONCLUSIONS
  Anti-beta2GPI antibodies were present in 28 of 57 primary APS patients (49%) and in 19 of 31 secondary APS patients (61%). The allele containing valine247 was significantly more frequent in primary APS patients with anti-beta2GPI antibodies than in controls (OR = 2.51, 95%, CI 1.03-6.13, P = 0.0396) or in primary APS patients without anti-beta2GPI antibodies (OR = 2.92, 95% CI 1.16-7.39, P = 0.0204). This tendency was not found in the secondary APS group. In conclusion, the beta2GPI polymorphism, valine/leucine247, is correlated with anti-beta2GPI antibody production in patients with primary APS, and valine247 may be important in the formation of beta2GPI antigenicity.
authors.affiliation: Department of Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Atsumi
authors.forename: A
authors.initials: A
authors.lastname: Tsutsumi
authors.forename: O
authors.initials: O
authors.lastname: Amengual
authors.forename: M A
authors.initials: MA
authors.lastname: Khamashta
authors.forename: G R
authors.initials: GR
authors.lastname: Hughes
authors.forename: Y
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: K
authors.initials: K
authors.lastname: Ichikawa
authors.forename: T
authors.initials: T
authors.lastname: Koike
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D053482:beta 2-Glycoprotein I
chemical_list: D001323:Autoantibodies; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I