title: Association between beta2-glycoprotein I gene polymorphisms and pediatric SLE and antiphospholipid antibodies.
abstract: Antibodies against phospholipids (PL) and PL-binding proteins have been causally implicated in antiphospholipid syndrome (APS). Mutations in the fifth domain of the beta2-glycoprotein I (beta2GPI) protein, a putative PL-binding site, may play a critical role in APS pathogenesis. The purpose of this study was to identify associations between beta2GPI mutations and both antiphospholipid antibodies (aPL) and their associated clinical manifestations in a pediatric and adolescent cohort and to search for novel mutations. Genetic analysis of beta2GPI was performed in 58 youths with systemic lupus erythematosus (SLE) and/or aPL, to identify known polymorphisms at amino acids 247 and 306 as well as novel mutations in exon 7 of the beta2GPI gene, and their association with aPL-associated clinical manifestations. Our results demonstrate an association between substitution of Val for Leu at AA247 (L247V) of beta2GPI and both the development of aPL (P = 0.05) and aPL-associated clinical manifestations (P = 0.03) among pediatric patients. The odds ratio associated with risk of aPL-associated clinical manifestations for the homozygous VV polymorphism was 5.5 (CI 1.3-23, P = 0.03) for the overall cohort, and 4.75 (CI 0.66-55.49, P = 0.06) after adjusting for ethnicity. The association was not significant after stratifying for SLE versus non-SLE. Association between the VV genotype at amino acid 247 of beta2GPI and clinical disease supports a genetic cause for APS among children and adolescents. Neither novel exon 7 beta2GPI mutations or the previously described C306G polymorphism was identified in this pediatric cohort.
authors.affiliation: Pediatric Rheumatology, University of California, San Francisco, CA 94143, USA. evonsche@peds.ucsf.edu
authors.forename: E
authors.initials: E
authors.lastname: von Scheven
authors.forename: M E
authors.initials: ME
authors.lastname: Elder
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D016736:Antiphospholipid Syndrome / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D008297:Male; D011110:Polymorphism, Genetic; D053482:beta 2-Glycoprotein I
chemical_list: D017152:Antibodies, Antiphospholipid; D018076:DNA, Complementary; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I