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Previously reported PDE3A–SLCO1C1 genetic variant does not correlate with anti-TNF response in a large UK rheumatoid arthritis cohort

    Samantha Louise Smith

    Arthritis Research UK, Centre for Genetics & Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK

    ,
    Darren Plant

    NIHR Manchester Musculoskeletal BRU, Central Manchester Foundation Trust & University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

    ,
    Xiu Hue Lee

    Arthritis Research UK, Centre for Genetics & Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK

    ,
    Jonathan Massey

    Arthritis Research UK, Centre for Genetics & Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK

    ,
    Kimme Hyrich

    Arthritis Research UK, Centre for Epidemiology, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK

    ,
    Ann W Morgan

    Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, UK

    ,
    Anthony G Wilson

    UCD School of Medicine & Medical Science, Conway Institute, University College Dublin, Dublin, Ireland

    ,
    John Isaacs

    NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne NHS Foundation Trust & Newcastle University, Newcastle-upon-Tyne, UK

    &
    Anne Bartonon behalf of BRAGGSS

    *Author for correspondence:

    E-mail Address: anne.barton@manchester.ac.uk

    Arthritis Research UK, Centre for Genetics & Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK

    NIHR Manchester Musculoskeletal BRU, Central Manchester Foundation Trust & University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

    :
    Published Online:https://doi.org/10.2217/pgs.16.16

    Aim: A genetic variant has recently reached genome-wide significance for association with TNF-inhibitor response in rheumatoid arthritis patients. Here we undertake a replication study in a UK Caucasian population to test for association with TNF-inhibitor response. Materials & methods: The genetic variant, rs3794271, located within the PDE3A–SLCO1C1 locus was analyzed for correlation with treatment response using both the EULAR classification criteria and absolute change in (Δ)DAS28 scores as outcome measures. Results: Genotype data were available from 1750 TNF-inhibitor treated individuals. However, no evidence for association was observed (EULAR: p = 0.91 and ΔDAS28: p = 0.93). Furthermore, no significant associations were observed upon stratification by the anti-TNF received (p > 0.05). Conclusion: In the largest replication cohort conducted to date, no evidence for association was observed.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 Liu C, Batliwalla F, Li W et al. Genome-wide association scan identifies candidate polymorphisms associated with differential response to anti-TNF treatment in rheumatoid arthritis. Mol. Med. 14(9–10), 575–81 (2008). • This was the first genome-wide association study to investigate biomarkers associated with response to anti-TNF biologics in rheumatoid arthritis.
    • 2 Plant D, Bowes J, Potter C et al. Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci. Arthritis Rheum. 63(3), 645–53 (2011). • Genome-wide association study conducted using a UK population of rheumatoid arthritis patients about to commence treatment with/currently receiving anti-TNF biologics.
    • 3 Krintel SB, Palermo G, Johansen JS et al. Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNFalpha inhibitors in patients with rheumatoid arthritis. Pharmacogenet. Genomics 22(8), 577–589 (2012). •• This genome-wide association study was the first to find evidence for association of rs3794271 with response to anti-TNF biologics in a Danish population and was the basis for a replication study conducted by Acosta Colman et al.
    • 4 Umicevic MM, Cui J, Vermeulen SH et al. Genome-wide association analysis of anti-TNF drug response in patients with rheumatoid arthritis. Ann. Rheum. Dis. 72(8), 1375–1381 (2013).
    • 5 Cui J, Stahl EA, Saevarsdottir S et al. Genome-wide association study and gene expression analysis identifies CD84 as a predictor of response to etanercept therapy in rheumatoid arthritis. PLoS Genet. 9(3), e1003394 (2013).
    • 6 Julià A, Fernandez-Nebro A, Blanco F et al. A genome-wide association study identifies a new locus associated with the response to anti-TNF therapy in rheumatoid arthritis. Pharmacogenomics J. 16(2), 147–150 (2016).
    • 7 Acosta-Colman I, Palau N, Tornero J et al. GWAS replication study confirms the association of PDE3A–SLCO1C1 with anti-TNF therapy response in rheumatoid arthritis. Pharmacogenomics 14(7), 727–734 (2013). •• This is the candidate replication study in which rs3794271 successfully replicated in a Spanish cohort of rheumatoid arthritis patients and where upon meta-analysis of both the Danish and Spanish cohorts, the association exceeded genome-wide significance thresholds for association.
    • 8 Potter C, Hyrich KL, Tracey A et al. Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not carriage of shared epitope or PTPN22 susceptibility variants, with anti-tumour necrosis factor response in rheumatoid arthritis. Ann. Rheum. Dis. 68(1), 69–74 (2009).
    • 9 Prevoo ML, van't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 38(1), 44–48 (1995).
    • 10 Purcell S, Neale B, Todd-Brown K et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81(3), 559–575 (2007).
    • 11 PLINK (version 1.07) 2007. http://pngu.mgh.harvard.edu/purcell/plink/.
    • 12 Quanto (version 1.2.4) 2009. http://hydra.usc.edu/gxe.
    • 13 Hyrich KL, Watson KD, Silman AJ, Symmons DP. Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford) 45(12), 1558–1565 (2006).
    • 14 van de Putte LB, Atkins C, Malaise M et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann. Rheum. Dis. 63(5), 508–516 (2004).
    • 15 Wells G, Becker JC, Teng J et al. Validation of the 28-joint Disease activity score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann. Rheum. Dis. 68(6), 954–960 (2009).
    • 16 Jurado RL. Why shouldn't we determine the erythrocyte sedimentation rate? Clin. Infect. Dis. 33(4), 548–549 (2001).