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

M. D. Wiese, N. Alotaibi, C. O'Doherty, M. J. Sorich, V. Suppiah, L. G. Cleland, S. M. Proudman

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Sulphasalazine (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.

Original languageEnglish
Pages (from-to)350-355
Number of pages6
JournalPharmacogenomics Journal
Volume14
Issue number4
DOIs
Publication statusPublished or Issued - Aug 2014

Keywords

  • ABCG2
  • N-acetyl transferase-2
  • pharmacogenomics
  • rheumatoid arthritis
  • sulphasalazine

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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