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PMID: 12145745 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus.

American journal of human genetics ·Vol. 71 ·No. 3 ·2002-09-00 ·Pages 543-53

Graham RR, Ortmann WA, Langefeld CD, Jawaheer D, Selby SA, Rodine PR, Baechler EC, Rohlf KE, Shark KB, Espe KJ, Green LE, Nair RP, Stuart PE, Elder JT, King RA, Moser KL, Gaffney PM, Bugawan TL, Erlich HA, Rich SS, Gregersen PK, Behrens TW

Abstract

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 approximately 500-kb region. We conclude that HLA class II haplotypes containing DRB1 and DQB1 alleles are strong risk factors for human SLE.

MeSH Terms
Alleles Case-Control Studies Founder Effect Genetic Predisposition to Disease Genotype HLA-DQ Antigens/genetics HLA-DQ beta-Chains HLA-DR Antigens/genetics HLA-DRB1 Chains Haplotypes/genetics Humans Linkage Disequilibrium Lod Score Lupus Erythematosus, Systemic/genetics Recombination, Genetic
Chemicals
HLA-DQ Antigens HLA-DQ beta-Chains HLA-DQB1 antigen HLA-DR Antigens HLA-DRB1 Chains HLA-DRB1*03:01 antigen
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Graham Robert R
Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
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
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/342290
Published
2002-09-00
Epub
2002-00-26
Pages
543-53
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC379191
Subset
IM
Grants
NCI NIH HHS · N01AR72232 · United States
NIAMS NIH HHS · P01-AR45231 · United States
NIAMS NIH HHS · R01-AR44222 · United States
NIAMS NIH HHS · N01-AR72232 · United States
NIAMS NIH HHS · R01 AR043274 · United States
NIAMS NIH HHS · R01-AR43274 · United States
Databases
OMIM
152700
External Links
PubMed source DOI: 10.1086/342290 PMC Full Text View journal details
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