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Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression.

Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression.

Authors :
Zelinkova Z
Derijks LJ
Stokkers PC
Vogels EW
van Kampen AH
Curvers WL
Cohn D
van Deventer SJ
Hommes DW
Source :
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association [Clin Gastroenterol Hepatol] 2006 Jan; Vol. 4 (1), pp. 44-9.
Publication Year :
2006

Abstract

Background & Aims: The use of azathioprine (AZA) in inflammatory bowel disease (IBD) patients is limited by toxicity, which occurs in up to 20% of treated patients. Mutations in the thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) genes have been associated with the occurrence of AZA-related toxicity. The aim of our study was to determine the relative contribution of ITPA and TPMT mutations to the development of toxicity induced by AZA treatment in IBD patients.<br />Methods: ITPA(94C>A, IVS2+21A>C) and TPMT (238G>C, 460G>A, and 719A>G) genotypes were assessed in 262 IBD patients (159 females, 103 males; 67 patients with ulcerative colitis, 195 patients with Crohn's disease) treated with AZA and were correlated with the development of leukopenia and hepatotoxicity.<br />Results: Leukopenia (leukocyte count, <3.0 x 10(9)/L) was observed in 4.6% of treated patients. The frequencies of mutant ITPA 94C>A and TPMT alleles were significantly higher in the leukopenic population compared with patients without leukopenia (16.7% and 5.4%, respectively, for ITPA 94C>A, and 20.8% and 4%, respectively, for TPMT). Moreover, the ITPA 94C>A and TPMT mutations predicted leukopenia: ITPA 94C>A odds ratio, 3.504; 95% confidence interval, 1.119-10.971 (P = .046); TPMT odds ratio, 6.316; 95% confidence interval, 2.141-18.634 (P = .004). Neither TPMT nor ITPA genotype predicted hepatotoxicity.<br />Conclusions: ITPA 94C>A and TPMT polymorphisms are associated with AZA-related leukopenia in IBD patients.

Details

Language :
English
ISSN :
1542-3565
Volume :
4
Issue :
1
Database :
MEDLINE
Journal :
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Publication Type :
Academic Journal
Accession number :
16431304
Full Text :
https://doi.org/10.1016/j.cgh.2005.10.019