title: High prevalence of polymorphism and low activity of thiopurine methyltransferase in patients with inflammatory bowel disease.
abstract: BACKGROUND
  Gene polymorphism of thiopurine methyltransferase (TPMT) correlates with decreased enzyme activity which determines a significant risk of adverse effect reactions (ADR) in patients treated with thiopurines. The aim of this study was to investigate TPMT genotype and phenotype status in patients with inflammatory bowel diseases (IBD).
  
  
  METHODS
  Fifty-one consecutive out-patients with IBD were genotyped for the following allelic variants: rs1800462 (referred as TPMT 2 allele), rs1800460 (referred as TPMT 3B allele), and 1142345 (referred as TPMT 3C allele). Red blood cell TPMT activity was measured using a competitive micro-well immunoassay for the 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% CI 2%-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 no differences 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.
  
  
  CONCLUSIONS
  Compared to the general population, IBD patients may have significantly higher prevalence of TPMT polymorphism and, even more, low activity. Phenotypic more than genotypic TPMT analysis could be useful to better manage IBD therapy with thiopurines.
authors.affiliation: Department of Health Science, University of Catanzaro "Magna Graecia", Catanzaro, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Larussa
authors.forename: Evelina
authors.initials: E
authors.lastname: Suraci
authors.forename: Margherita
authors.initials: M
authors.lastname: Lentini
authors.forename: Immacolata
authors.initials: I
authors.lastname: Nazionale
authors.forename: Luigia
authors.initials: L
authors.lastname: Gallo
authors.forename: Ludovico
authors.initials: L
authors.lastname: Abenavoli
authors.forename: Maria
authors.initials: M
authors.lastname: Imeneo
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Costanzo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cuda
authors.forename: Francesco
authors.initials: F
authors.lastname: Luzza
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D003424:Crohn Disease / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D004342:Drug Hypersensitivity / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D015995:Prevalence; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase