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- DOI: 10.1097/FPC.0b013e32833878d7
- PMID: 20300049
- UKPMCID: 20300049
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Polymorphisms spanning the TNFR2 and TACE genes do not contribute towards variable anti-TNF treatment response.
Potter, Catherine; Gibbons, Laura J J; Bowes, John D D; Cordell, Heather J J; Hyrich, Kimme; Isaacs, John D D; Morgan, Ann W W; Wilson, Anthony G G; Barton, Anne; BRAGGSS
Pharmacogenetics and genomics. 2010;20(5):338-341.
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Full-text held externally
- DOI: 10.1097/FPC.0b013e32833878d7
- PMID: 20300049
- UKPMCID: 20300049
Abstract
The introduction of tumour necrosis factor antagonists (anti-TNF) has greatly improved the treatment of rheumatoid arthritis, however, a significant proportion of patients fail to respond to therapy. We hypothesized that variants spanning the type 2 TNF receptor (TNFR2) and the TNF cleavage enzyme (TACE) genes contribute towards the observed variation in patient response (defined as the absolute change in 28-joint count disease activity score). Twenty-nine single nucleotide polymorphisms (SNPs) were genotyped in a large cohort of patients (n=602) and analysed by multivariate linear regression. Three SNPs (rs520916, rs652625, rs597519) mapping upstream of TNFR2 showed borderline evidence for association (P<0.1) across the complete cohort and, more so, in the etanercept-treated subgroup. However, the evidence of association was neither replicated in an independent cohort (n=377) nor strengthened after combined analysis (n=979). We conclude that common SNPs spanning the TNFR2 and TNF cleavage enzyme (TACE) genes do not have a major effect on the response to anti-TNF therapy in rheumatoid arthritis patients.