Prahalad S, Ryan M H, Shear E S, Thompson S D, Giannini E H, Glass D N
Children's Hospital Medical Center, University of Cincinnati College of Medicine, Ohio 45229-3039, USA.
Arthritis Rheum. 2000 Oct;43(10):2335-8. doi: 10.1002/1529-0131(200010)43:10<2335::AID-ANR22>3.0.CO;2-W.
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).
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.
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).
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.
在一组患病同胞对（ASP）中，通过发病和病程类型分层，检测HLA区域与青少年类风湿性关节炎（JRA）之间的连锁关系。
对在JRA ASP研究注册库（由美国国立关节炎、肌肉骨骼和皮肤病研究所赞助）登记的80对患有JRA的同胞进行HLA - DR分型。通过拟合优度卡方检验，将观察到的无、一个或两个亲本DR等位基因共享比例与预期比例1:2:1进行比较。通过Fisher精确检验，一组265名无关对照受试者作为患者中HLA - DR等位基因频率的比较人群。
总体而言，患有JRA的ASP中存在两个DR等位基因的过度共享。观察到的共享0、1或2个DR等位基因的比例为8:40:32，而不是预期比例20:40:20（P < 0.001）。按JRA发病类型分层时，发病类型一致的ASP中显示出等位基因过度共享（P = 0.002）。少关节型和多关节型发病均如此。按病程分层时，病程一致的ASP中也显示出等位基因过度共享（P < 0.001）。少关节型和多关节型病程均如此。在共享两个DR等位基因的32对ASP中，5对同时具有DR8和DR11，这比对照组（n = 0）中的发生率显著更高（P < 0.0001）。
这项对独立的多基因家族队列的研究证实了先前报道的少关节型JRA与HLA - DR区域之间的连锁关系，该连锁关系在单基因家族队列中使用不同的分析方法得以确定。此外，本研究为多关节型JRA与HLA - DR区域之间的连锁关系建立了证据。
