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Pharmacogenetics of thiopurine therapy in paediatric IBD patients

L De Ridder1, J M Van Dieren, H J H Van Deventer

  • 1Department of Paediatric Gastroenterology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands. l.deridder@amc.uva.nl

Alimentary Pharmacology & Therapeutics
|April 14, 2006
PubMed

Insights

Genetic variations in TPMT and ITPase enzymes do not appear to predict azathioprine adverse events in pediatric inflammatory bowel disease patients. Therefore, routine genetic testing before thiopurine therapy is not recommended.

Area of Science:

  • Pediatric Gastroenterology
  • Pharmacogenetics
  • Inflammatory Bowel Disease

Background:

  • Azathioprine is a common treatment for pediatric inflammatory bowel disease.
  • Adverse events may be linked to thiopurine S-methyltransferase (TPMT) and inosine triphophate pyrophosphatase (ITPase) enzyme activity.

Purpose of the Study:

  • To investigate the frequencies of functional TPMT and ITPA gene polymorphisms.
  • To determine the association between these polymorphisms and adverse events in children with inflammatory bowel disease receiving azathioprine.

Main Methods:

  • Genotyping for TPMT and ITPA polymorphisms was performed on 72 pediatric patients with inflammatory bowel disease treated with azathioprine.
  • Adverse events were recorded and analyzed in relation to identified genetic variations.

Main Results:

  • Eleven patients (15.3%) experienced adverse events leading to azathioprine discontinuation, including pancreatitis, leucopenia, and general malaise.
  • Ten of these 11 patients had wild-type alleles for the investigated genotypes.
  • Two homozygous patients for ITPA 94C>A polymorphisms tolerated azathioprine well.

Conclusions:

  • No significant association was found between functional TPMT or ITPA polymorphisms and the occurrence of azathioprine-related adverse events.
  • Pharmacogenetic assessment before initiating thiopurine therapy is not currently deemed necessary for this patient population.
Abstract

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