RAPID COMMUNICATIONInvestigation of genetic variants within candidate genes of the TNFRSF1B signalling pathway on the response to anti-TNF agents in a UK cohort of rheumatoid arthritis patientsBowes, John D.a; Potter, Catherinee; Gibbons, Laura J.a; Hyrich, Kimmea; Plant, Darrena; Morgan, Ann W.c; Wilson, Anthony G.d; Isaacs, John D.e; Worthington, Janea; Barton, AnneaBRAGGSSAuthor Information aArthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester bBiologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cLeeds Institute of Molecular Medicine, University of Leeds, Leeds dSection of Musculoskeletal Sciences, University of Sheffield, Sheffield eInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK Correspondence to John D. Bowes, BSc, Arthritis Research Campaign Epidemiology Unit, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK Tel: +44 161 2751677; fax: +44 161 2755043; e-mail: [email protected] See appendix for list of members of the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate. Received 18 August 2008 Accepted 5 January 2009 Pharmacogenetics and Genomics: April 2009 - Volume 19 - Issue 4 - p 319-323 doi: 10.1097/FPC.0b013e328328d51f Buy Metrics Abstract The introduction of anti-tumour necrosis factor (TNF) agents has greatly improved the treatment of rheumatoid arthritis; however, a significant proportion of patients fail to respond to therapy. We hypothesized that genes within the TNF receptor superfamily member 1B signalling pathway contribute towards the observed variation in patient response. This was tested by genotyping 73 single-nucleotide polymorphisms (SNPs) from six candidate genes (DUSP1, HRB, IKBKAP, MAP3K1, MAP3K14 and TANK) in a large UK cohort of rheumatoid arthritis patients (n=642). Two SNPs [rs96844 (MAP3K1) and rs4792847 (MAP3K14)] showed evidence of association (P<0.05) to treatment response and were subsequently examined in an independent cohort of patients (n=428). Replication of association to either SNP was not achieved, but combined analysis of the complete cohort (n=1070) provided nominal evidence of association to both SNPs. We conclude that analysis of the common variation in the selected candidate genes did not provide strong evidence to implicate their involvement in varying patient response to anti-TNF treatment. © 2009 Lippincott Williams & Wilkins, Inc.