Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus
Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus
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DOI：
10.1086/342290
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发表时间：
2002-09-01
影响因子：
9.8
通讯作者：
Behrens, TW
中科院分区：
文献类型：
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作者：
Graham, RR;Ortmann, WA;Behrens, TW
人类白细胞抗原（HLA） I类和II类等位基因是许多自身免疫性疾病的遗传危险因素。然而，HLA基因座在人类系统性红斑狼疮（SLE）中的作用尚不清楚。利用大量SLE家族HLA区域的多态微卫星密集图谱，我们确定了三种不同的单倍型，它们包含II类区域并表现出传输扭曲。对创始人DRB1和DQB1分型结果显示，3个单倍型分别含有DRB1*1501/DQB1*0602、DRB1*0801/DQB1*0402和DRB1*0301/DQB1*0201等位基因。通过可视化祖先重组，我们将包含DRB1*1501和DRB1*0801的疾病相关单倍型缩小到500 kb区域。我们得出结论，含有DRB1和DQB1等位基因的HLA II类单倍型是人类SLE的强危险因素。
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 DRB1*1501/DQB1*0602, DRB1*0801/DQB1*0402, and DRB1*0301/DQB1*0201 alleles, respectively. By visualizing ancestral recombinants, we narrowed the disease-associated haplotypes containing DRB1*1501 and DRB1*0801 to an 500-kb region. We conclude that HLA class II haplotypes containing DRB1 and DQB1 alleles are strong risk factors for human SLE.