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De Ridder, L. et al.

De Ridder, Van Dieren, Van Deventer, Stokkers, Van der Woude, Van Vuuren, Benninga, Escher, Hommes,

Pharmacogenetics of thiopurine therapy in paediatric IBD patients.

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.[1]

References

Pharmacogenetics of thiopurine therapy in paediatric IBD patients. De Ridder, L., Van Dieren, J.M., Van Deventer, H.J., Stokkers, P.C., Van der Woude, J.C., Van Vuuren, A.J., Benninga, M.A., Escher, J.C., Hommes, D.W. Aliment. Pharmacol. Ther. (2006) [Pubmed]

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