title: Juvenile rheumatoid arthritis: linkage to HLA demonstrated by allele sharing in affected sibpairs.
abstract: OBJECTIVE
  To test for linkage between the HLA region and juvenile rheumatoid arthritis (JRA), with stratification by onset and course types, in a cohort of affected sibling pairs (ASPs).
  
  
  METHODS
  Eighty pairs of siblings with JRA who were registered with the Research Registry for JRA ASPs (sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases) were typed for HLA-DR. The observed 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 for 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, instead of the expected ratio of 20:40:20 (P < 0.001). When stratified by JRA onset type, excess allele sharing was demonstrated among ASPs who were concordant for onset type (P = 0.002). This was true for both pauciarticular and polyarticular onset. When stratified by disease course, excess allele sharing was also demonstrated among ASPs who were concordant for disease course (P < 0.001). This was true for both the pauciarticular and the polyarticular course. Among the 32 ASPs who shared two DR alleles, 5 pairs had both DR8 and DR11, which was significantly more frequent (P < 0.0001) than the incidence in the control group (n = 0).
  
  
  CONCLUSIONS
  This study of an independent cohort of multiplex families confirms 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 linkage between polyarticular JRA and the HLA-DR region.
authors.affiliation: Children's Hospital Medical Center, University of Cincinnati College of Medicine, Ohio 45229-3039, USA.
authors.forename: S
authors.initials: S
authors.lastname: Prahalad
authors.forename: M H
authors.initials: MH
authors.lastname: Ryan
authors.forename: E S
authors.initials: ES
authors.lastname: Shear
authors.forename: S D
authors.initials: SD
authors.lastname: Thompson
authors.forename: E H
authors.initials: EH
authors.lastname: Giannini
authors.forename: D N
authors.initials: DN
authors.lastname: Glass
mesh_terms: D000483:Alleles; D001171:Arthritis, Juvenile / Q000235:genetics; D015331:Cohort Studies; D004200:Diseases in Twins / Q000235:genetics; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male
chemical_list: D006680:HLA Antigens