Juvenile rheumatoid arthritis - Linkage to HLA demonstrated by allele sharing in affected sibpairs

Objective, To test for linkage between the HLA region and juvenile rheumato id arthritis (JRA), with stratification by onset and course types, in a coh ort of affected sibling pairs (ASPs), Methods, Eighty pairs of siblings with JRA who were registered with the Res earch Registry for JRA ASPs (sponsored by the National Institute of Arthrit is and Musculoskeletal and Skin Diseases) were typed for HLA-DR. The observ ed ratio of sharing of none, one, or both parental DR alleles was compared against the expected ratio of 1:2:1 by goodness-of-fit chi-square tests, A group of 265 unrelated control subjects served as a comparison population f or HLA-DR allele frequencies among patients, by Fisher's exact test, Results, Overall, there was excess sharing of 2 DR alleles among ASPs with JRA, The observed ratio of sharing 0, 1, or 2 DR alleles was 8:40:32, inste ad of the expected ratio of 20:40:20 (P < 0.001). When stratified by JRA on set type, excess allele sharing was demonstrated among ASPs who were concor dant for onset type (P = 0.002). This was true for both pauciarticular and polyarticular onset, When stratified by disease course, excess allele shari ng was also demonstrated among ASPs who were concordant for disease course (P < 0.001). This was true for both the pauciarticular and the polyarticula r course. Among the 32 ASPs who shared two DR alleles, 5 pairs had both DRS and DR11, which was significantly more frequent (P < 0.0001) than the inci dence in the control group (n = 0). Conclusion, This study of an independent cohort of multiplex families confi rms the previously reported linkage between pauciarticular JRA and the HLA- DR region that was identified using a different analytic method in a cohort of simplex families, Additionally, this study establishes evidence for lin kage between polyarticular JRA and the HLA-DR region.