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Testing the role of vitamin D in response to antitumour necrosis factor α therapy in a UK cohort: a Mendelian randomisation approach
  1. Annie Yarwood1,
  2. Sebastien Viatte1,
  3. Darren Plant2,
  4. Ann W Morgan3,4,
  5. John Isaacs5,
  6. Anthony G Wilson6,
  7. Kimme Hyrich1,
  8. Steve Eyre1,
  9. Anne Barton1,2,
  10. Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS)
  1. 1Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK
  2. 2NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester Partnership, Manchester, UK
  3. 3NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, The Leeds Teaching Hospitals NHS Trust, Leeds, UK
  4. 4Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, St. James's University Hospital, Leeds, UK
  5. 5NIHR Newcastle Biomedical Research Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle-upon-Tyne, UK
  6. 6Department of Infection and Immunity, University of Sheffield Medical School, Sheffield, UK
  1. Correspondence to Professor Anne Barton, Arthritis Research UK Epidemiology Unit, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK; anne.barton{at}

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Approximately 30% of rheumatoid arthritis (RA) patients fail to respond to anti-tumour necrosis factor (anti-TNF) treatment;1 hence, the ability to predict which patients will respond to treatment would represent a major clinical advance. Vitamin D has been implicated in many autoimmune diseases including RA; in addition, vitamin D has been shown to induce TNFα production by some immune cells leading to the hypothesis that vitamin D levels may influence anti-TNF treatment response.2 ,3 Several studies have now confirmed the association of genetic variants within four vitamin D metabolism genes (GC, DHCR7/NADSYN1, CYP2R1, CYP24A1) with circulating vitamin D levels in healthy controls.4 ,5 In addition, single nucleotide polymorphisms (SNPs) in these genes have also been associated with autoimmune diseases.6 The association of the same variants in the same genes that control circulating levels of vitamin D with response to anti-TNF treatment provides an unbiased test of the hypothesis that vitamin D levels are important in response to these therapies (Mendelian randomisation).7 We, therefore, investigated the effect of vitamin D on response to anti-TNF therapy, testing six SNPs previously associated with circulating levels of vitamin D4 ,5 for association with response to anti-TNF therapy in RA patients from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) cohort (table 1), which includes patients recruited across the UK.8 SNPs were selected to capture by linkage disequilibrium (LD) (r2>0.8) 94.26% of SNPs previously associated with vitamin D levels in two previous studies.4 ,5 Multivariate linear and logistic regression was used to assess the effects of each SNP on treatment response measured by absolute change in Disease Activity Score in 28 joints (DAS28) over 6 months9 (n=1396) or in poor (n=237) versus good (n=322) responders according to European League …

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