Amino Acid Position 11 of HLA-DRβ1 is a Major Determinant of Chromosome 6p Association with Ulcerative Colitis

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Amino Acid Position 11 of HLA-DRβ1 is a Major Determinant of Chromosome 6p Association with Ulcerative Colitis

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Title: Amino Acid Position 11 of HLA-DRβ1 is a Major Determinant of Chromosome 6p Association with Ulcerative Colitis
Author: Achkar, Jean-Paul; Klei, Lambertus; de Bakker, Paul I Wen; Bellone, Gaia; Rebert, Nancy; Scott, Regan; Lu, Ying; Regueiro, Miguel; Brzezinski, Aaron; Kamboh, M. Ilyas; Fiocchi, Claudio; Devlin, Bernie; Trucco, Massimo; Ringquist, Steven; Roeder, Kathryn; Duerr, Richard H

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Citation: Achkar, Jean-Paul, Lambertus Klei, Paul I.W. de Bakker, Gaia Bellone, Nancy Rebert, Regan Scott, Ying Lu, et al. 2012. Amino acid position 11 of HLA-DRβ1 is a major determinant of chromosome 6p association with ulcerative colitis. Genes and Immunity 13(3): 245-252.
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Abstract: The major histocompatibility complex (MHC) on chromosome 6p is an established risk locus for ulcerative colitis (UC) and Crohn’s disease (CD). We aimed to better define MHC association signals in UC and CD by combining data from dense single nucleotide polymorphism (SNP) genotyping and from imputation of classical HLA types, their constituent SNPs and corresponding amino acids in 562 UC, 611 CD, and 1,428 control subjects. Univariate and multivariate association analyses were performed, controlling for ancestry. In univariate analyses, absence of the rs9269955 C allele was strongly associated with risk for UC (P = 2.67×\(10^{-13}\)). rs9269955 is a SNP in the codon for amino acid position 11 of HLA-DRβ1, located in the P6 pocket of the HLA-DR antigen binding cleft. This amino acid position was also the most significantly UC-associated amino acid in omnibus tests (P = 2.68×\(10^{-13}\)). Multivariate modeling identified rs9269955-C and 13 other variants in best predicting UC versus control status. In contrast, there was only suggestive association evidence between the MHC and CD. Taken together, these data demonstrate that variation at HLA-DRβ1, amino acid 11 in the P6 pocket of the HLA-DR complex antigen binding cleft is a major determinant of chromosome 6p association with ulcerative colitis.
Published Version: doi:10.1038/gene.2011.79
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341846/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10531920
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