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Enrichment of Vitamin D response elements in RA associated loci supports a role for vitamin D in the pathogenesis of RA

The aim of this study was to explore the role of vitamin-D in rheumatoid arthritis (RA) pathogenesis by investigating enrichment of vitamin-D response elements (VDREs) in confirmed RA susceptibility loci and testing variants associated with vitamin-D levels for association with RA. Bioinformatically...

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Autores principales: Yarwood, Annie, Martin, Paul, Bowes, John, Lunt, Mark, Worthington, Jane, Barton, Anne, Eyre, Steve
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736318/
https://www.ncbi.nlm.nih.gov/pubmed/23636220
http://dx.doi.org/10.1038/gene.2013.23
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author Yarwood, Annie
Martin, Paul
Bowes, John
Lunt, Mark
Worthington, Jane
Barton, Anne
Eyre, Steve
author_facet Yarwood, Annie
Martin, Paul
Bowes, John
Lunt, Mark
Worthington, Jane
Barton, Anne
Eyre, Steve
author_sort Yarwood, Annie
collection PubMed
description The aim of this study was to explore the role of vitamin-D in rheumatoid arthritis (RA) pathogenesis by investigating enrichment of vitamin-D response elements (VDREs) in confirmed RA susceptibility loci and testing variants associated with vitamin-D levels for association with RA. Bioinformatically, VDRE genomic positions were overlaid with non HLA confirmed RA susceptibility regions. The number of VDREs at RA loci was compared to a randomly selected set of genomic loci to calculate an average relative risk (RR). SNPs in the DHCR7/NADSYN1 and CYP2R1 loci, previously associated with circulating vitamin-D levels, were tested in UK RA cases (n = 3870) and controls (n = 8430). Significant enrichment of VDREs was seen at RA loci (p=9.23×10(−8)) when regions were defined either by gene (RR 5.50) or position (RR 5.86). SNPs in the DHCR7/NADSYN1 locus showed evidence of positive association with RA, rs4944076 (p=0.008, OR 1.14 95% CI 1.03-1.24). The significant enrichment of VDREs at RA associated loci and the modest association of variants in loci controlling levels of circulating vitamin-D, supports the hypothesis that vitamin-D plays a role in the development of RA.
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spelling pubmed-37363182014-01-01 Enrichment of Vitamin D response elements in RA associated loci supports a role for vitamin D in the pathogenesis of RA Yarwood, Annie Martin, Paul Bowes, John Lunt, Mark Worthington, Jane Barton, Anne Eyre, Steve Genes Immun Article The aim of this study was to explore the role of vitamin-D in rheumatoid arthritis (RA) pathogenesis by investigating enrichment of vitamin-D response elements (VDREs) in confirmed RA susceptibility loci and testing variants associated with vitamin-D levels for association with RA. Bioinformatically, VDRE genomic positions were overlaid with non HLA confirmed RA susceptibility regions. The number of VDREs at RA loci was compared to a randomly selected set of genomic loci to calculate an average relative risk (RR). SNPs in the DHCR7/NADSYN1 and CYP2R1 loci, previously associated with circulating vitamin-D levels, were tested in UK RA cases (n = 3870) and controls (n = 8430). Significant enrichment of VDREs was seen at RA loci (p=9.23×10(−8)) when regions were defined either by gene (RR 5.50) or position (RR 5.86). SNPs in the DHCR7/NADSYN1 locus showed evidence of positive association with RA, rs4944076 (p=0.008, OR 1.14 95% CI 1.03-1.24). The significant enrichment of VDREs at RA associated loci and the modest association of variants in loci controlling levels of circulating vitamin-D, supports the hypothesis that vitamin-D plays a role in the development of RA. 2013-05-02 2013-07 /pmc/articles/PMC3736318/ /pubmed/23636220 http://dx.doi.org/10.1038/gene.2013.23 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Yarwood, Annie
Martin, Paul
Bowes, John
Lunt, Mark
Worthington, Jane
Barton, Anne
Eyre, Steve
Enrichment of Vitamin D response elements in RA associated loci supports a role for vitamin D in the pathogenesis of RA
title Enrichment of Vitamin D response elements in RA associated loci supports a role for vitamin D in the pathogenesis of RA
title_full Enrichment of Vitamin D response elements in RA associated loci supports a role for vitamin D in the pathogenesis of RA
title_fullStr Enrichment of Vitamin D response elements in RA associated loci supports a role for vitamin D in the pathogenesis of RA
title_full_unstemmed Enrichment of Vitamin D response elements in RA associated loci supports a role for vitamin D in the pathogenesis of RA
title_short Enrichment of Vitamin D response elements in RA associated loci supports a role for vitamin D in the pathogenesis of RA
title_sort enrichment of vitamin d response elements in ra associated loci supports a role for vitamin d in the pathogenesis of ra
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736318/
https://www.ncbi.nlm.nih.gov/pubmed/23636220
http://dx.doi.org/10.1038/gene.2013.23
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