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Imputing Variants in HLA-DR Beta Genes Reveals That HLA-DRB1 Is Solely Associated with Rheumatoid Arthritis and Systemic Lupus Erythematosus

Authors
Kim, K | Bang, SY | Yoo, DH | Cho, SK | Choi, CB | Sung, YK | Kim, TH | Jun, JB | Kang, YM | Suh, CH  | Shim, SC | Lee, SS | Lee, J | Chung, WT | Kim, SK | Choe, JY | Nath, SK | Lee, HS | Bae, SC
Citation
PloS one, 11(2). : e0150283-e0150283, 2016
Journal Title
PloS one
ISSN
1932-6203
Abstract
The genetic association of HLA-DRB1 with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is well documented, but association with other HLA-DR beta genes (HLA-DRB3, HLA-DRB4 and HLA-DRB5) has not been thoroughly studied, despite their similar functions and chromosomal positions. We examined variants in all functional HLA-DR beta genes in RA and SLE patients and controls, down to the amino-acid level, to better understand disease association with the HLA-DR locus. To this end, we improved an existing HLA reference panel to impute variants in all protein-coding HLA-DR beta genes. Using the reference panel, HLA variants were inferred from high-density SNP data of 9,271 RA-control subjects and 5,342 SLE-control subjects. Disease association tests were performed by logistic regression and log-likelihood ratio tests. After imputation using the newly constructed HLA reference panel and statistical analysis, we observed that HLA-DRB1 variants better accounted for the association between MHC and susceptibility to RA and SLE than did the other three HLA-DRB variants. Moreover, there were no secondary effects in HLA-DRB3, HLA-DRB4, or HLA-DRB5 in RA or SLE. Of all the HLA-DR beta chain paralogs, those encoded by HLA-DRB1 solely or dominantly influence susceptibility to RA and SLE.
MeSH

DOI
10.1371/journal.pone.0150283
PMID
26919467
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Rheumatology
Ajou Authors
서, 창희
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