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Association between ß2-glycoprotein I gene polymorphisms and pediatric SLE and antiphospholipid antibodies

Pediatric Rheumatology, University of California, San Francisco, CA, USA, evonsche{at}peds.ucsf.edu

M E Elder

Pediatric Immunology, Rheumatology, and Infectious Diseases, University of Florida, Gainesville, FL, USA

Antibodies against phospholipids (PL) and PL-binding proteins have been causally implicated in antiphospholipid syndrome (APS). Mutations in the fifth domain of the ß₂-glycoprotein I (ß₂GPI) protein, a putative PL-binding site, may play a critical role in APS pathogenesis. The purpose of this study was to identify associations between ß₂GPI 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 ß₂GPI 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 ß₂GPI gene, and their association with aPL-associated clinical manifestations.

Our results demonstrate an association between substitution of Val for Leu at AA247 (L247V) of ß₂GPI 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 ß₂GPI and clinical disease supports a genetic cause for APS among children and adolescents. Neither novel exon 7 ß₂GPI mutations or the previously described C306G polymorphism was identified in this pediatric cohort.

Key Words: antiphospholipid syndrome • ß2-glycoprotein I • children • genetic • SLE

Lupus, Vol. 14, No. 6, 440-444 (2005)
DOI: 10.1191/0961203305lu2126oa


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