A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis

Andreu, Antoni L., Field, Judith, Browning, Sharon R., Johnson, Laura J., Danoy, Patrick, Varney, Michael D., Tait, Brian D., Gandhi, Kaushal S., Charlesworth, Jac C., Heard, Robert N., Stewart, Graeme J., Kilpatrick, Trevor J., Foote, Simon J., Bahlo, Melanie, Butzkueven, Helmut, Wiley, James, Booth, David R., Taylor, Bruce V., Brown, Matthew A., Rubio, Justin P., Stankovich, Jim, & Griffiths, Lyn R. (2010) A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis. PLoS ONE, 5(10), e13454-e13454.

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Abstract

We conducted an association study across the human leukocyte antigen (HLA) complex to identify loci associated with multiple sclerosis (MS). Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each ). All associations were significant in an independent replication cohort of 2212 cases and 2251 controls () and were highly significant in the combined dataset (). The associated SNPs included proxies for HLA-DRB115:01 and HLA-DRB103:01, and SNPs in moderate linkage disequilibrium (LD) with HLA-A02:01, HLA-DRB104:01 and HLA-DRB113:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set , replication set , combined ). HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB103:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association.

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ID Code: 62588
Item Type: Journal Article
Refereed: Yes
DOI: 10.1371/journal.pone.0013454
ISSN: 1932-6203
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2010 Public Library of Science
Deposited On: 17 Sep 2013 03:46
Last Modified: 24 Nov 2016 03:01

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