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Vitamin D has an important immunoregulatory function,1 ,2 and there is suggestive evidence for its role in the aetiology of autoimmune diseases, including rheumatoid arthritis (RA).3 Vitamin D levels are reduced in individuals with severe RA,4 ,5 but it is difficult to determine whether this reduction is cause or effect. The onset of arthritis during winter is associated with greater radiographic progression at 6 months, which would be compatible with a causative role.6 Single nucleotide polymorphisms (SNPs) in four vitamin D metabolism genes (GC, DHCR7/NADSYN1, CYP2R1 and CYP24A1) are associated at genome-wide significance with circulating vitamin D levels.7 ,8 Since vitamin D level is associated with RA severity, an association between those SNPs and RA severity would establish causality. Testing the association of genetic variants in genes that control circulating vitamin D levels provides, therefore, an instrument to obtain an unbiased test of the hypothesis that vitamin D levels are aetiologically linked to RA outcome by controlling unmeasured confounding (Mendelian randomisation9). Hence, we tested SNPs previously associated with vitamin D metabolism,7 ,8 and SNPs in these …
Contributors Data cleaning: SV and SA-M. Statistical analysis: SV and BF. SNP selection for genotyping: A Yarwood. Genotyping: KMA and EF. Study design: AB. Writing the manuscript: SV. Manuscript preparation and interpretation of the results: All authors. NOAR study lead: DPMS and AB. ERAS study lead: A Young.
Competing interests None.
Patient consent Obtained.
Ethics approval ERAS received ethical approval from the West Hertfordshire Local Research Ethics Committee and subsequently from the Caldicott Guardian. Informed consent was obtained from all patients. Ethical approval for the study was obtained (MREC 99/8/84), and informed consent was signed by all patients.
Provenance and peer review Not commissioned; externally peer reviewed.
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