期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 71, 期 3, 页码 543-553出版社
UNIV CHICAGO PRESS
DOI: 10.1086/342290
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资金
- NCI NIH HHS [N01AR72232] Funding Source: Medline
- NIAMS NIH HHS [P01-AR45231, R01 AR043274, R01-AR44222, N01-AR72232, R01-AR43274] Funding Source: Medline
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.
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