OBJECTIVE: To elucidate the relative importance of the HLA-DR and HLA-DQ loci in conferring genetic predisposition to rheumatoid arthritis (RA). METHODS: HLA-DRB1 and HLA-DQB1 alleles were typed in a set of 685 patients with RA using sequence-specific polymerase chain reaction. Allele and phenotype frequencies were compared with those in 2 large sets of historical, ethnically matched healthy controls, using the relative predispositional effect method. RESULTS: Positive association was confirmed with the shared epitope positive HLA-DRB1 alleles associated with RA in Caucasians. A significant susceptibility effect was observed with HLA-DRB1*09, described in other ethnically diverse populations but not in Caucasians. A significant underrepresentation of the HLA-DRB1*0103 variant was noted among the RA cases, supporting the proposed protective role of the DERAA motif at residues 70-74 of the DRbeta molecule. No HLA-DRB1 independent association of the HLA-DQB1 alleles, implicated in predisposing to RA, was evident. CONCLUSION: These data corroborate the shared epitope hypothesis of susceptibility to RA and provide strong evidence for the DRB1 locus as the primary RA susceptibility factor in the HLA region.
OBJECTIVE: To elucidate the relative importance of the HLA-DR and HLA-DQ loci in conferring genetic predisposition to rheumatoid arthritis (RA). METHODS:HLA-DRB1 and HLA-DQB1 alleles were typed in a set of 685 patients with RA using sequence-specific polymerase chain reaction. Allele and phenotype frequencies were compared with those in 2 large sets of historical, ethnically matched healthy controls, using the relative predispositional effect method. RESULTS: Positive association was confirmed with the shared epitope positive HLA-DRB1 alleles associated with RA in Caucasians. A significant susceptibility effect was observed with HLA-DRB1*09, described in other ethnically diverse populations but not in Caucasians. A significant underrepresentation of the HLA-DRB1*0103 variant was noted among the RA cases, supporting the proposed protective role of the DERAA motif at residues 70-74 of the DRbeta molecule. No HLA-DRB1 independent association of the HLA-DQB1 alleles, implicated in predisposing to RA, was evident. CONCLUSION: These data corroborate the shared epitope hypothesis of susceptibility to RA and provide strong evidence for the DRB1 locus as the primary RA susceptibility factor in the HLA region.
Authors: Laura B Hughes; Dahliann Morrison; James M Kelley; Miguel A Padilla; L Kelly Vaughan; Andrew O Westfall; Harshit Dwivedi; Ted R Mikuls; V Michael Holers; Lezlie A Parrish; Graciela S Alarcón; Doyt L Conn; Beth L Jonas; Leigh F Callahan; Edwin A Smith; Gary S Gilkeson; George Howard; Larry W Moreland; Nick Patterson; David Reich; S Louis Bridges Journal: Arthritis Rheum Date: 2008-02
Authors: Jason H Karnes; Christian M Shaffer; Lisa Bastarache; Silvana Gaudieri; Andrew M Glazer; Heidi E Steiner; Jonathan D Mosley; Simon Mallal; Joshua C Denny; Elizabeth J Phillips; Dan M Roden Journal: PLoS One Date: 2017-02-16 Impact factor: 3.240
Authors: Joyce J B C van Beers; Annemiek Willemze; Judith Stammen-Vogelzangs; Jan W Drijfhout; René E M Toes; Ger J M Pruijn Journal: Arthritis Res Ther Date: 2012-02-17 Impact factor: 5.156