Meta-analysis: Inosine triphosphate pyrophosphatase polymorphisms and thiopurine toxicity in the treatment of inflammatory bowel disease.
BACKGROUND
Thiopurines are widely used for the treatment of inflammatory bowel disease, but are associated with the development of side effects. It has been suggested that the enzyme inosine triphosphate pyrophosphatase (ITPA) plays a role in the digestion of thiopurines and that defective activity resulting from polymorphisms in the inosine triphosphate pyrophosphatase encoding genes may be associated with thiopurine-induced side effects. Current studies are controversial regarding this hypothesis.


OBJECTIVE
To perform a meta-analysis and gain more insight into a possible correlation between thiopurine-induced side effects and ITPA polymorphisms.


METHODS
We explored Medline for articles on ITPA polymorphisms and thiopurine toxicity. Studies that compared ITPA polymorphism frequencies among thiopurine-tolerant and -intolerant adult inflammatory bowel disease patients were included in this meta-analysis.


RESULTS
Nine published studies investigated associations between ITPA polymorphisms and thiopurine toxicity. Six studies (with 751 patients included) met our inclusion criteria and were processed in the meta-analysis. This analysis demonstrates that the ITPA 94C-->A polymorphism, is not significantly associated with any of the studied side effect parameters.


CONCLUSIONS
This meta-analysis does not prove a correlation between the development of thiopurine toxicity and the ITPA 94C-->A polymorphism. This implies that there is no clinical relevance to determine ITPA polymorphisms in thiopurine-treated patients.
Van Dieren
J M
JM
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. j.vandieren@erasmusmc.nl
Hansen
B E
BE
Kuipers
E J
EJ
Nieuwenhuis
E E S
EE
Van der Woude
C J
CJ
D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008297:Male; D008780:Methyltransferases / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011755:Pyrophosphatases / Q000009:adverse effects*; D000097630:Inosine Triphosphatase
D008780:Methyltransferases; D011755:Pyrophosphatases; D000097630:Inosine Triphosphatase; C022745:thiopurine methyltransferase