The telomeric part of the HLA region predisposes to rheumatoid arthritis independently of the class II loci

We have evaluated the possible contribution of genes besides DQ and DR to t he association of HLA with rheumatoid arthritis (RA). To this end, we have looked at the allele distributions of six microsatellites, D6S1014, D6S2673 , TNF alpha, MID, C1-2-5, and C1-3-2 among 132 RA patients and 254 controls . We have defined 19 microsatellite clusters corresponding to previously de scribed ancestral haplotypes. One of them was D6S1014*143-D6S273*133-TNF al pha *99-MIB*350-C1-2-5*196-C1-3-2*354, often found associated with DQB1*020 1-DRB1*0301. As part of this microsatellite cluster, the allele MIB*350 was found to be a RA-predisposing factor, independent of DRB1*0301 and RA-pred isposing haplotypes DQB1*03-DRB1*04 and DQB1*0501-DRB1*01. We conclude that the telomeric part of the HLA region contains a locus conferring predispos ition to RA independently of HLA class II. Human Immunology 62,!, 75-84 (20 01). (C) American Society for Histocompatability and Immunogenetics, 2001. Published by Elsevier Science Inc.