title: Genetic polymorphisms of thiopurine S-methyltransferase in a cohort of patients with systemic autoimmune diseases.
abstract: OBJECTIVE
  Azathioprine (AZA) is a purine antimetabolite, prodrug widely used as a disease modifying drug in several rheumatic conditions. The aim of the present study was to evaluate the prevalence of TPMT genetic polymorphisms in a cohort of Italian Caucasian patients affected by rheumatic diseases and treated with AZA, and to establish correlations with the tolerability of AZA treatment.
  
  
  RESULTS
  Seventy-eight Caucasian patients, 16 males and 62 females, median age 41 years (min-max: 24-76) were enrolled. At the time of evaluation, the median duration of treatment with AZA was 8 months (min-max: 2-150 months); the median dose of AZA per kg of body weight was 1.42 mg (min-max: 0.5-2). Among the 78 patients evaluated, 76 presented a wild type genotype (TPMT *1), while polymorphic alleles were identified in 2 patients (2.6%). Twenty-five patients (32%) experienced different types of adverse events (AE) under AZA treatment. Eighteen patients (23.1%) discontinued AZA because of AE. No correlation was observed between polymorphic TPMT alleles and the development of AE.
  
  
  CONCLUSIONS
  Our analysis supports the view that TPMT genotyping alone is not sufficient to adequately personalize the AZA dosage in rheumatic patients. Further studies based on phenotypic analysis of TPMT enzyme and assay of AZA metabolite appear to be required.
authors.affiliation: Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tani
authors.forename: M
authors.initials: M
authors.lastname: Mosca
authors.forename: R
authors.initials: R
authors.lastname: Colucci
authors.forename: G
authors.initials: G
authors.lastname: Gori
authors.forename: A
authors.initials: A
authors.lastname: d'Ascanio
authors.forename: N
authors.initials: N
authors.lastname: Ghisu
authors.forename: M
authors.initials: M
authors.lastname: Fornai
authors.forename: A
authors.initials: A
authors.lastname: Di Paolo
authors.forename: C
authors.initials: C
authors.lastname: Blandizzi
authors.forename: M
authors.initials: M
authors.lastname: Del Tacca
authors.forename: S
authors.initials: S
authors.lastname: Bombardieri
mesh_terms: D000328:Adult; D000368:Aged; D000963:Antimetabolites / Q000009:adverse effects* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000235:genetics*; D001379:Azathioprine / Q000009:adverse effects* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People; D055815:Young Adult
chemical_list: D000963:Antimetabolites; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine