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- DOI: 10.1002/art.33381
- PMID: 21952740
- UKPMCID: 21952740
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Investigation of established rheumatoid-arthritis (RA) susceptibility genetic markers as predictors of response to anti-TNF therapy in a large UK cohort replicates association with the PTPRC gene.
Plant, Darren; Prajapati, Rita; Hyrich, Kimme L; Morgan, Ann W; Wilson, Anthony G; Isaacs, John D; BRAGGSS; Barton, Anne
Arthritis and rheumatism. 2012;64(3):665-670.
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Full-text held externally
- DOI: 10.1002/art.33381
- PMID: 21952740
- UKPMCID: 21952740
Abstract
BACKGROUND: Several rheumatoid arthritis (RA) susceptibility variants map close to genes involved in the TNF signalling pathway, prompting the investigation of RA susceptibility variants in studies of predictors of response to TNF-blockade. A previous study has reported association with the PTPRC genetic locus and the aim of the current study was to test established RA susceptibility variants, including PTPRC, in the prediction of response to TNF-blockade in a large cohort of UK patients. METHODS: DNA samples from 1,115 UK RA patients receiving anti-TNF biologic therapy were analysed for 29 single nucleotide polymorphisms (SNPs) previously established as RA susceptibility variants. In the primary analysis, linear regression of change in DAS28 at 6 months follow-up was conducted for each SNP using an additive model. In a secondary analysis, logistic regression models were used to compare patients with good (n=274) versus poor (n=195) response, as defined using the EULAR response criteria. Results were combined with those from previous studies using meta-analysis. RESULTS: The PTPRC (rs10919563) SNP was associated with improved treatment response in both the primary (coef 0.19, 95% CI 0.09 to 0.37, P=0.04) and secondary (OR 0.62, 95% CI 0.40 to 0.95, P=0.03) analysis. Meta-analysis with a previous study strengthened the evidence for association (P=5.13×10(-5) ). No convincing association between other candidate loci and treatment response was detected. CONCLUSION: The rs10919563 RA susceptibility variant at the PTPRC gene locus predicts improved anti-TNF response. Fine mapping studies are required to determine whether this or another variant at the locus provides the greatest predictive accuracy. © 2011 American College of Rheumatology.