Pharmacogenetics of thiopurines in inflammatory bowel disease.

Abstract:

:Thiopurines are widely used in the treatment of inflammatory bowel disease (IBD). However, in clinical practice azathioprine (AZA) or 6-mercaptopurine (6-MP) are not effective in one-third of patients and up to one-fifth of patients discontinue thiopurine therapy due to adverse reactions. The observed interindividual differences in therapeutic response and toxicity to thiopurines are explained to a large extent by the variable formation of active metabolites, which is at least partly caused by genetic polymorphisms of the genes encoding crucial enzymes in thiopurine metabolism. In this in-depth review we discuss the genetic polymorphisms of genes encoding for glutathione S-tranferases, xanthine oxidase, thiopurine S-methyltransferase, inosine triphosphate pyrophosphatase, hypoxanthine phosphoribosyltransferase, inosine monophosphate dehydrogenase and multidrug resistance proteins. Pharmacogenetic knowledge in this field has increased dramatically and is still rapidly increasing, but the translation into practical guidelines with tailored advices will cost much effort in the near future.

journal_name

Curr Pharm Des

authors

Derijks LJ,Wong DR

doi

10.2174/138161210790112773

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

145-54

issue

2

eissn

1381-6128

issn

1873-4286

pii

CPD-Luc J.J. Derijks (Guchelaar)

journal_volume

16

pub_type

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