Pharmacogenetics of thiopurine therapy in paediatric IBD patients
Article first published online: 16 MAR 2006
Alimentary Pharmacology & Therapeutics
Volume 23, Issue 8, pages 1137–1141, April 2006
How to Cite
DE RIDDER, L., VAN DIEREN, J. M., VAN DEVENTER, H. J. H., STOKKERS, P. C. F., VAN DER WOUDE, J. C. J., VAN VUUREN, A. J., BENNINGA, M. A., ESCHER, J. C. and HOMMES, D. W. (2006), Pharmacogenetics of thiopurine therapy in paediatric IBD patients. Alimentary Pharmacology & Therapeutics, 23: 1137–1141. doi: 10.1111/j.1365-2036.2006.02853.x
- Issue published online: 30 MAR 2006
- Article first published online: 16 MAR 2006
- Publication data Submitted 14 December 2005 First decision 10 January 2006 Resubmitted 23 January 2006 Accepted 23 January 2006
Background Azathioprine is widely used in the treatment of children with inflammatory bowel disease. The occurrence and type of adverse events to azathioprine may be related to thiopurine S-methyltransferase (TPMT) enzyme activity and to inosine triphophate pyrophosphatase (ITPase) deficiency.
Aim Investigate frequencies of functional TPMT polymorphisms and ITPA polymorphisms and their association with the occurrence of adverse events during azathioprine therapy in a paediatric inflammatory bowel disease population.
Methods Seventy-two azathioprine treated paediatric inflammatory bowel disease patients, 47% girls, mean age 12.5 years (range 6.5–17.5), were assessed for TPMT and ITPA polymorphisms and for adverse events. The relation between polymorphisms and adverse events is evaluated.
Results Of all azathioprine treated patients, 11 experienced an adverse event for which azathioprine was stopped: pancreatitis (n = 4), leucopenia (n = 2) and ‘general malaise’ (n = 5). Of the 11 patients who stopped azathioprine because of adverse events, 10 had wild-type alleles for all investigated genotypes. Genotyping of ITPA 94C>A polymorphisms showed that two patients were homozygous, both tolerated azathioprine well.
Conclusions No association of functional ITPA and TPMT polymorphisms and the occurrence of azathioprine related adverse events could be detected. Pharmacogenetic assessment prior to thiopurine therapy does not seem warranted.