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Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis

Title
Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis
Author
배상철
Issue Date
2012-01
Publisher
NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
Citation
NATURE GENETICS, 권: 44, 호: 3, 페이지: 291-U91
Abstract
The genetic association of the major histocompatibility complex (MHC) to rheumatoid arthritis risk has commonly been attributed to alleles in HLA-DRB1. However, debate persists about the identity of the causal variants in HLA-DRB1 and the presence of independent effects elsewhere in the MHC. Using existing genome-wide SNP data in 5,018 individuals with seropositive rheumatoid arthritis (cases) and 14,974 unaffected controls, we imputed and tested classical alleles and amino acid polymorphisms in HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1 and HLA-DRB1, as well as 3,117 SNPs across the MHC. Conditional and haplotype analyses identified that three amino acid positions (11, 71 and 74) in HLA-DR beta 1 and single-amino-acid polymorphisms in HLA-B (at position 9) and HLA-DP beta 1 (at position 9), which are all located in peptide-binding grooves, almost completely explain the MHC association to rheumatoid arthritis risk. This study shows how imputation of functional variation from large reference panels can help fine map association signals in the MHC.
URI
https://www.nature.com/articles/ng.1076
ISSN
1061-4036
DOI
10.1038/ng.1076
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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