TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease

G. Stocco, S. Martelossi, A. Barabino, M. Fontana, P. Lionetti, G. Decorti, N. Malusà, F. Bartoli, M. Fezzi, T. Giraldi, A. Ventura

Research output: Contribution to journalArticle

Abstract

Background: Thiopurines are used in the treatment of inflammatory bowel disease. They are metabolised via methylation by thiopurine-S-methyltransferase (TPMT), which displays a genetically determined polymorphic activity. Subjects with reduced TPMT activity have a higher concentration of active thiopurine metabolites and may be at increased risk of bone-marrow suppression. Aims: To evaluate the relevance of TPMT genotyping in the management of thiopurines therapy in inflammatory bowel disease patients. Patients and methods: Adverse effects and clinical response were determined retrospectively and correlated with TPMT genotype in 70 paediatric inflammatory bowel disease patients. Results: Nineteen patients (27.1%) developed adverse effects; of the 51 who did not, 34 (66.7%) responded to treatment. Five patients (7.1%) were heterozygous for a variant TPMT allele; two of these (40%) were intolerant to thiopurines, compared to 17 of the 65 patients (26.2%) with a wild type gene (O.R. 1.88, 95% CI 0.29-12.2, p = 0.61); among the 34 responders, the median dosage of the drug required to obtain remission was lower for mutated than for wild type patients (1.6 mg kg-1 day-1 versus 2.0 mg kg-1 day-1, p = 0.043). Conclusions: There was no significant association between adverse effects of thiopurines and TPMT heterozygous genotype, but TPMT genotyping could be useful in establishing the most appropriate dose of thiopurines to start treatment.

Original languageEnglish
Pages (from-to)940-945
Number of pages6
JournalDigestive and Liver Disease
Volume37
Issue number12
DOIs
Publication statusPublished - Dec 2005

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thiopurine methyltransferase
Inflammatory Bowel Diseases
Genotype
Pediatrics
Therapeutics
Methylation
Bone Marrow
Alleles

Keywords

  • Genotyping
  • Inflammatory bowel disease
  • Thiopurine-S-methyl transferase
  • Thiopurines (azathioprine, 6-mercaptopurine)

ASJC Scopus subject areas

  • Gastroenterology

Cite this

TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease. / Stocco, G.; Martelossi, S.; Barabino, A.; Fontana, M.; Lionetti, P.; Decorti, G.; Malusà, N.; Bartoli, F.; Fezzi, M.; Giraldi, T.; Ventura, A.

In: Digestive and Liver Disease, Vol. 37, No. 12, 12.2005, p. 940-945.

Research output: Contribution to journalArticle

Stocco, G, Martelossi, S, Barabino, A, Fontana, M, Lionetti, P, Decorti, G, Malusà, N, Bartoli, F, Fezzi, M, Giraldi, T & Ventura, A 2005, 'TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease', Digestive and Liver Disease, vol. 37, no. 12, pp. 940-945. https://doi.org/10.1016/j.dld.2005.08.003
Stocco, G. ; Martelossi, S. ; Barabino, A. ; Fontana, M. ; Lionetti, P. ; Decorti, G. ; Malusà, N. ; Bartoli, F. ; Fezzi, M. ; Giraldi, T. ; Ventura, A. / TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease. In: Digestive and Liver Disease. 2005 ; Vol. 37, No. 12. pp. 940-945.
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abstract = "Background: Thiopurines are used in the treatment of inflammatory bowel disease. They are metabolised via methylation by thiopurine-S-methyltransferase (TPMT), which displays a genetically determined polymorphic activity. Subjects with reduced TPMT activity have a higher concentration of active thiopurine metabolites and may be at increased risk of bone-marrow suppression. Aims: To evaluate the relevance of TPMT genotyping in the management of thiopurines therapy in inflammatory bowel disease patients. Patients and methods: Adverse effects and clinical response were determined retrospectively and correlated with TPMT genotype in 70 paediatric inflammatory bowel disease patients. Results: Nineteen patients (27.1{\%}) developed adverse effects; of the 51 who did not, 34 (66.7{\%}) responded to treatment. Five patients (7.1{\%}) were heterozygous for a variant TPMT allele; two of these (40{\%}) were intolerant to thiopurines, compared to 17 of the 65 patients (26.2{\%}) with a wild type gene (O.R. 1.88, 95{\%} CI 0.29-12.2, p = 0.61); among the 34 responders, the median dosage of the drug required to obtain remission was lower for mutated than for wild type patients (1.6 mg kg-1 day-1 versus 2.0 mg kg-1 day-1, p = 0.043). Conclusions: There was no significant association between adverse effects of thiopurines and TPMT heterozygous genotype, but TPMT genotyping could be useful in establishing the most appropriate dose of thiopurines to start treatment.",
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T1 - TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease

AU - Stocco, G.

AU - Martelossi, S.

AU - Barabino, A.

AU - Fontana, M.

AU - Lionetti, P.

AU - Decorti, G.

AU - Malusà, N.

AU - Bartoli, F.

AU - Fezzi, M.

AU - Giraldi, T.

AU - Ventura, A.

PY - 2005/12

Y1 - 2005/12

N2 - Background: Thiopurines are used in the treatment of inflammatory bowel disease. They are metabolised via methylation by thiopurine-S-methyltransferase (TPMT), which displays a genetically determined polymorphic activity. Subjects with reduced TPMT activity have a higher concentration of active thiopurine metabolites and may be at increased risk of bone-marrow suppression. Aims: To evaluate the relevance of TPMT genotyping in the management of thiopurines therapy in inflammatory bowel disease patients. Patients and methods: Adverse effects and clinical response were determined retrospectively and correlated with TPMT genotype in 70 paediatric inflammatory bowel disease patients. Results: Nineteen patients (27.1%) developed adverse effects; of the 51 who did not, 34 (66.7%) responded to treatment. Five patients (7.1%) were heterozygous for a variant TPMT allele; two of these (40%) were intolerant to thiopurines, compared to 17 of the 65 patients (26.2%) with a wild type gene (O.R. 1.88, 95% CI 0.29-12.2, p = 0.61); among the 34 responders, the median dosage of the drug required to obtain remission was lower for mutated than for wild type patients (1.6 mg kg-1 day-1 versus 2.0 mg kg-1 day-1, p = 0.043). Conclusions: There was no significant association between adverse effects of thiopurines and TPMT heterozygous genotype, but TPMT genotyping could be useful in establishing the most appropriate dose of thiopurines to start treatment.

AB - Background: Thiopurines are used in the treatment of inflammatory bowel disease. They are metabolised via methylation by thiopurine-S-methyltransferase (TPMT), which displays a genetically determined polymorphic activity. Subjects with reduced TPMT activity have a higher concentration of active thiopurine metabolites and may be at increased risk of bone-marrow suppression. Aims: To evaluate the relevance of TPMT genotyping in the management of thiopurines therapy in inflammatory bowel disease patients. Patients and methods: Adverse effects and clinical response were determined retrospectively and correlated with TPMT genotype in 70 paediatric inflammatory bowel disease patients. Results: Nineteen patients (27.1%) developed adverse effects; of the 51 who did not, 34 (66.7%) responded to treatment. Five patients (7.1%) were heterozygous for a variant TPMT allele; two of these (40%) were intolerant to thiopurines, compared to 17 of the 65 patients (26.2%) with a wild type gene (O.R. 1.88, 95% CI 0.29-12.2, p = 0.61); among the 34 responders, the median dosage of the drug required to obtain remission was lower for mutated than for wild type patients (1.6 mg kg-1 day-1 versus 2.0 mg kg-1 day-1, p = 0.043). Conclusions: There was no significant association between adverse effects of thiopurines and TPMT heterozygous genotype, but TPMT genotyping could be useful in establishing the most appropriate dose of thiopurines to start treatment.

KW - Genotyping

KW - Inflammatory bowel disease

KW - Thiopurine-S-methyl transferase

KW - Thiopurines (azathioprine, 6-mercaptopurine)

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