HLA associations of anti-beta2 glycoprotein I response in a Greek cohort with antiphospholipid syndrome and meta-analysis of four ethnic groups

Using molecular typing, we evaluated the strength of class II HLA associati ons in 67 Greek patients with antiphospholipid syndrome (APS), 54 of whom h ad antibodies against beta 2-glycoprotein I (beta 2GPI), as compared to 246 controls. To further clarify and delineate HLA associations of the beta 2G PI response, we combined these data with individual patient data From three other ethnic groups including an additional 74 patients with beta 2GPI res ponse and 403 ethnically matched controls of white, African-American, and M exican-American origin in a Formal meta-analysis. The major alleles associa ted with anti-beta 2GPI response are HLA-DQA1*03 (in particular *0301) and the HLA-DRB1*1302-DQB1*0604 haplotype, while protection against developing an anti-beta 2GPI response is related primarily to the HLA-DRB1*0101-DQA1*0 101 haplotype and the the HLA-DRB1*1101 allele. These effects are not signi ficantly heterogeneous across ethnic groups. The previously observed associ ation with HLA-DQB1*0302 may simply reflect linkage disequilibrium with HLA -DQA1*0301 and the previously reported HLA-DQB1*06 effect is limited to HLA -DQB1*0604/0605, while HLA-DQB1*0602 is unlikely to be important. The metaa nalysis clearly documents that the anti-beta 2GPI response is determined by a few specific class II alleles and haplotypes. (C) American Society for H istocompatibility and Immunogenetics, 1999. Published by Elsevier Science I nc.