BACKGROUND: Gene polymorphism of thiopurine methyltransferase (TPMT) correlateswith decreased enzyme activity which determines a significant risk of adverseeffect reactions (ADR) in patients treated with thiopurines. The aim of thisstudy was to investigate TPMT genotype and phenotype status in patients withinflammatory bowel diseases (IBD).METHODS: Fifty-one consecutive out-patients with IBD were genotyped for thefollowing allelic variants: rs1800462 (referred as TPMT 2 allele), rs1800460(referred as TPMT 3B allele), and 1142345 (referred as TPMT 3C allele). Red bloodcell TPMT activity was measured using a competitive micro-well immunoassay forthe semi-quantitative determination of TPMT activity in red blood cells (RBC) by means of a 6-MP substrate.RESULTS: Polymorphism of TPMT was found in 5 out of 51 patients (10%; 95% CI2%-18%), three heterozygous and two homozygous carriers. Six patients (11.8%; 95%CI 2.4%-19.5%) displayed very low, 12 (23.5%; 95% CI 11.4%-34.5%) intermediate,and 33 (64.7%; 95% CI 52%-78%) normal/high TPMT activity. There were nodifferences between TPMT genotype and phenotype groups according to age, type of disease, smoking, and chronic medications. A 71% (95% CI 61%-81%; κ=0.45)concordance rate was found between genotype and phenotype status. Six out of 27(22%) current or past users of azathioprine developed ADR, with three (50%)displaying TPMT genotype and/or phenotype alterations.CONCLUSION: Compared to the general population, IBD patients may havesignificantly higher prevalence of TPMT polymorphism and, even more, lowactivity. Phenotypic more than genotypic TPMT analysis could be useful to better manage IBD therapy with thiopurines.

High prevalence of polymorphism and low activity of thiopurine methyltransferase in patients with inflammatory bowel disease.

Larussa T;Montebianco Abenavoli L;LUZZA F;Cuda G;Costanzo F
2012-01-01

Abstract

BACKGROUND: Gene polymorphism of thiopurine methyltransferase (TPMT) correlateswith decreased enzyme activity which determines a significant risk of adverseeffect reactions (ADR) in patients treated with thiopurines. The aim of thisstudy was to investigate TPMT genotype and phenotype status in patients withinflammatory bowel diseases (IBD).METHODS: Fifty-one consecutive out-patients with IBD were genotyped for thefollowing allelic variants: rs1800462 (referred as TPMT 2 allele), rs1800460(referred as TPMT 3B allele), and 1142345 (referred as TPMT 3C allele). Red bloodcell TPMT activity was measured using a competitive micro-well immunoassay forthe semi-quantitative determination of TPMT activity in red blood cells (RBC) by means of a 6-MP substrate.RESULTS: Polymorphism of TPMT was found in 5 out of 51 patients (10%; 95% CI2%-18%), three heterozygous and two homozygous carriers. Six patients (11.8%; 95%CI 2.4%-19.5%) displayed very low, 12 (23.5%; 95% CI 11.4%-34.5%) intermediate,and 33 (64.7%; 95% CI 52%-78%) normal/high TPMT activity. There were nodifferences between TPMT genotype and phenotype groups according to age, type of disease, smoking, and chronic medications. A 71% (95% CI 61%-81%; κ=0.45)concordance rate was found between genotype and phenotype status. Six out of 27(22%) current or past users of azathioprine developed ADR, with three (50%)displaying TPMT genotype and/or phenotype alterations.CONCLUSION: Compared to the general population, IBD patients may havesignificantly higher prevalence of TPMT polymorphism and, even more, lowactivity. Phenotypic more than genotypic TPMT analysis could be useful to better manage IBD therapy with thiopurines.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12317/7844
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 10
social impact