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Polymorphisms spanning the TNFR2 and TACE genes do not contribute towards variable anti-TNF treatment response

Lookup NU author(s): Professor Heather Cordell, Professor John Isaacs

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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. Pharmacogenetics and Genomics 20: 338-341 (c) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.


Publication metadata

Author(s): Potter C, Gibbons LJ, Bowes JD, Cordell HJ, Hyrich K, Isaacs JD, Morgan AW, Wilson AG, Barton A, Biol Rheumatoid Arthrit Genetics Group

Publication type: Article

Publication status: Published

Journal: Pharmacogenetics and Genomics

Year: 2010

Volume: 20

Issue: 5

Pages: 338-341

Print publication date: 01/05/2010

ISSN (print): 1744-6872

ISSN (electronic): 1744-6880

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1097/FPC.0b013e32833878d7

DOI: 10.1097/FPC.0b013e32833878d7


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