Graham Robert R, Ortmann Ward A, Langefeld Carl D, Jawaheer Damini, Selby Scott A, Rodine Peter R, Baechler Emily C, Rohlf Kristine E, Shark Katherine B, Espe Karl J, Green Linda E, Nair Rajan P, Stuart Philip E, Elder James T, King Richard A, Moser Kathy L, Gaffney Patrick M, Bugawan Teodorica L, Erlich Henry A, Rich Stephen S, Gregersen Peter K, Behrens Timothy W
Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
Am J Hum Genet. 2002 Sep;71(3):543-53. doi: 10.1086/342290. Epub 2002 Jul 26.
Human leukocyte antigen (HLA) class I and class II alleles are implicated as genetic risk factors for many autoimmune diseases. However, the role of the HLA loci in human systemic lupus erythematosus (SLE) remains unclear. Using a dense map of polymorphic microsatellites across the HLA region in a large collection of families with SLE, we identified three distinct haplotypes that encompassed the class II region and exhibited transmission distortion. DRB1 and DQB1 typing of founders showed that the three haplotypes contained DRB11501/ DQB10602, DRB10801/ DQB10402, and DRB10301/DQB10201 alleles, respectively. By visualizing ancestral recombinants, we narrowed the disease-associated haplotypes containing DRB11501 and DRB10801 to an approximately 500-kb region. We conclude that HLA class II haplotypes containing DRB1 and DQB1 alleles are strong risk factors for human SLE.
人类白细胞抗原(HLA)I类和II类等位基因被认为是许多自身免疫性疾病的遗传风险因素。然而,HLA基因座在人类系统性红斑狼疮(SLE)中的作用仍不清楚。我们在一大组SLE家族中使用跨越HLA区域的多态微卫星密集图谱,确定了三种不同的单倍型,它们涵盖II类区域并表现出传递失真。对创始人的DRB1和DQB1分型显示,这三种单倍型分别包含DRB11501/DQB10602、DRB10801/DQB10402和DRB10301/DQB10201等位基因。通过可视化祖先重组体,我们将包含DRB11501和DRB10801的疾病相关单倍型缩小到大约500 kb的区域。我们得出结论,包含DRB1和DQB1等位基因的HLA II类单倍型是人类SLE的强风险因素。