Rheumatoid arthritis, genes and vitamin D

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

Genes and Immunity , (2 May 2013) | doi:10.1038/gene.2013.23

A Yarwood, P Martin, J Bowes, M Lunt, J Worthington, A Barton and S Eyre

The aim of this study was to explore the role of vitamin D in rheumatoid arthritis (RA) pathogenesis by investigating the 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 (human leukocyte antigen)-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).

Single-nucleotide polymorphisms (SNPs) in the DHCR7/NADSYN1 (nicotinamide adenine dinucleotide synthase 1) 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, odds ratio (OR) 1.14, 95% confidence interval (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 has a role in the development of RA.

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