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 language | English |
|---|---|
| Pages (from-to) | 940-945 |
| Number of pages | 6 |
| Journal | Digestive and Liver Disease |
| Volume | 37 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2005 |
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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 journal › Article
}
TY - JOUR
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)
UR - http://www.scopus.com/inward/record.url?scp=33644873301&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644873301&partnerID=8YFLogxK
U2 - 10.1016/j.dld.2005.08.003
DO - 10.1016/j.dld.2005.08.003
M3 - Article
C2 - 16202677
AN - SCOPUS:33644873301
VL - 37
SP - 940
EP - 945
JO - Digestive and Liver Disease
JF - Digestive and Liver Disease
SN - 1590-8658
IS - 12
ER -