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Thiopurinemethyltransferase (TPMT) genotype and TPMT activity in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: relation to azathioprine maintenance treatment and adverse effects
  1. P M Stassen1,
  2. R P H Derks2,
  3. C G M Kallenberg2,
  4. C A Stegeman1
  1. 1
    Department of Nephrology, University Medical Centre Groningen, University of Groningen, The Netherlands
  2. 2
    Department of Clinical Immunology, University Medical Center Groningen, University of Groningen, The Netherlands
  1. P M Stassen, Department of Internal Medicine, Maastricht University Medical Center, The Netherlands; p.stassen{at}mumc.nl

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Azathioprine is used in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to maintain remission. Azathioprine is inactivated and converted into hepatotoxic metabolites by the enzyme thiopurine methyltransferase (TPMT). Polymorphisms in the gene encoding TPMT lead to differences in activity of the enzyme. In our patients with AAV, we determined the prevalence of variant TPMT genotypes and abnormal TPMT activity, and investigated the relationship between TPMT and the efficacy and toxicity of azathioprine.

Patients newly diagnosed with AAV between 1995 and 2006, who were initially treated with cyclophosphamide and corticosteroids followed by azathioprine, were included and followed for 47 months. All patients were treated without knowledge of their TPMT status. Data were retrospectively retrieved …

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