Pharmacogenomics of NAT2 and ABCG2 influence the toxicity and efficacy of sulphasalazine containing DMARD regimens in early rheumatoid arthritis

Simple item page
dc.contributor.authorWiese, M.
dc.contributor.authorAlotaibi, N.
dc.contributor.authorO'Doherty, C.
dc.contributor.authorSorich, M.
dc.contributor.authorSuppiah, V.
dc.contributor.authorCleland, L.
dc.contributor.authorProudman, S.
dc.date.issued2014
dc.description.abstractSulphasalazine (SSA) is a disease modifying anti-rheumatic drug (DMARD) that is commonly used to treat rheumatoid arthritis (RA). Plasma levels of SSA and its metabolite sulphapyridine are influenced by common polymorphisms in genes that encode N-acetyl transferase 2 (NAT2) and ATP-binding cassette protein G2 (ABCG2). Study participants had early RA that was treated with a combination DMARD regimen that included SSA. Toxicity was defined by cessation of SSA due to adverse effects and response as remission after 12 months of treatment. The effect of variables on toxicity was assessed by a Cox-proportional Hazard model and response by logistic regression. After correction for conventional variables, toxicity in 229 participants was influenced by NAT2 phenotype (hazard ratio=1.74 (95% confidence interval (CI) 1.01-3.21), P=0.044) and remission in 141 participants was associated with ABCG2 genotype (odds ratio=3.34 (95% CI 1.18-9.50), P=0.024). In our sample of early RA patients who were primarily treated with a combination of DMARDs, common variants in genes that encode NAT2 and ABCG2 were associated respectively with toxicity and response to SSA.
dc.description.statementofresponsibilityMD Wiese, N Alotaibi, C O’Doherty, MJ Sorich, V Suppiah, LG Cleland and SM Proudman
dc.identifier.citationPharmacogenomics Journal, 2014; 14(4):350-355
dc.identifier.doi10.1038/tpj.2013.45
dc.identifier.issn1470-269X
dc.identifier.issn1473-1150
dc.identifier.orcidSuppiah, V. [0000-0001-5496-935X]
dc.identifier.orcidProudman, S. [0000-0002-3046-9884]
dc.identifier.urihttp://hdl.handle.net/2440/114669
dc.language.isoen
dc.publisherNature Publishing Group
dc.rights© 2014 Macmillan Publishers Limited All rights reserved
dc.source.urihttps://doi.org/10.1038/tpj.2013.45
dc.subjectABCG2; N-acetyl transferase-2; pharmacogenomics; rheumatoid arthritis; sulphasalazine
dc.titlePharmacogenomics of NAT2 and ABCG2 influence the toxicity and efficacy of sulphasalazine containing DMARD regimens in early rheumatoid arthritis
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Medicine publications