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The HLA-DRβ1 amino acid positions 11-13-26 explain the majority of SLE-MHC associations.
- Source :
-
Nature communications [Nat Commun] 2014 Dec 23; Vol. 5, pp. 5902. Date of Electronic Publication: 2014 Dec 23. - Publication Year :
- 2014
-
Abstract
- Genetic association of the major histocompatibility complex (MHC) locus is well established in systemic lupus erythematosus (SLE), but the causal functional variants in this region have not yet been discovered. Here we conduct the first fine-mapping study, which thoroughly investigates the SLE-MHC associations down to the amino acid level of major HLA genes in 5,342 unrelated Korean case-control subjects, taking advantages of HLA imputation with a newly constructed Asian HLA reference panel. The most significant association is mapped to amino acid position 13 of HLA-DRβ1 (P=2.48 × 10(-17)) and its proxy position 11 (P=4.15 × 10(-17)), followed by position 26 in a stepwise conditional analysis (P=2.42 × 10(-9)). Haplotypes defined by amino acid positions 11-13-26 support the reported effects of most classical HLA-DRB1 alleles in Asian and European populations. In conclusion, our study identifies the three amino acid positions at the epitope-binding groove of HLA-DRβ1 that are responsible for most of the association between SLE and MHC.
- Subjects :
- Alleles
Amino Acid Motifs
Case-Control Studies
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
HLA-DRB1 Chains chemistry
HLA-DRB1 Chains genetics
Haplotypes
Humans
Lupus Erythematosus, Systemic genetics
Male
Protein Binding
Republic of Korea
Asian People genetics
HLA-DRB1 Chains metabolism
Lupus Erythematosus, Systemic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 25533202
- Full Text :
- https://doi.org/10.1038/ncomms6902