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Open AccessArticle

Correlation between Thiopurine S-Methyltransferase Genotype and Adverse Events in Inflammatory Bowel Disease Patients

1
Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy
2
Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
3
Department of Medical Sciences, Unit of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
4
Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, 10124 Turin, Italy
5
Department of Health Sciences, University “Magna Graecia”, viale Europa, 88100 Catanzaro, Italy
*
Author to whom correspondence should be addressed.
Medicina 2019, 55(8), 441; https://doi.org/10.3390/medicina55080441
Received: 17 April 2019 / Revised: 30 July 2019 / Accepted: 31 July 2019 / Published: 5 August 2019
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Abstract

Background and Objectives: In patients with inflammatory bowel diseases (IBD), the use of azathioprine results in adverse events at a rate of 5% to 20%. The aim of the study was to assess a possible correlation between genetic variability of the enzyme thiopurine S-methyltransferase (TPMT) and the development of toxicity to azathioprine. Materials and Methods: A retrospective, single center, blind, case-control study was conducted on 200 IBD patients, of whom 60 cases suspended azathioprine due to toxicity (leukopenia, pancreatitis, hepatitis, and nausea or vomiting), and 140 controls continued treatment with the drug without adverse events. Results: In the entire cohort, only 8 cases of heterozygous mutations of TPMT were observed, corresponding to 4% mutated haplotype rate, much lower than that reported in literature (close to 10%). No homozygous mutation was found. Regarding the TPMT allelic variants, we did not find any statistically significant difference between patients who tolerated azathioprine and those who suffered from adverse events. (OR = 0.77, 95% CI = 0.08–7.72; p = 0.82). Conclusions: According to our study, in IBD patients, the search for TPMT gene mutations before starting treatment with azathioprine is not helpful in predicting the occurrence of adverse events. Importantly, patients with allelic variants should not be denied the therapeutic option of azathioprine, as they may tolerate this drug. View Full-Text
Keywords: Crohn’s disease; inflammatory bowel disease; large intestine; small intestine; ulcerative colitis Crohn’s disease; inflammatory bowel disease; large intestine; small intestine; ulcerative colitis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Ribaldone, D.G.; Adriani, A.; Caviglia, G.P.; De Nicolò, A.; Agnesod, D.; Simiele, M.; Riganò, D.; Pellicano, R.; Canaparo, R.; Di Perri, G.; D’Avolio, A.; Luzza, F.; Abenavoli, L.; Saracco, G.M.; Astegiano, M. Correlation between Thiopurine S-Methyltransferase Genotype and Adverse Events in Inflammatory Bowel Disease Patients. Medicina 2019, 55, 441.

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