title: Polymorphism of ITPA 94C>A and risk of adverse effects among patients with acute lymphoblastic leukaemia treated with 6-mercaptopurine.
abstract: OBJECTIVE
  Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA 94C>A) contribute to variable responses, including fatal adverse effects, among subjects treated with 6-mercaptopurine (6-MP). Our objectives were to investigate the distribution of specific TPMT and ITPA genotypes in healthy subjects and patients with acute lymphoblastic leukaemia (ALL) from the three main ethnic groups (Malays, Chinese and Indians) in Malaysia and the association of the polymorphisms with adverse effects of 6-MP.
  
  
  METHODS
  Patients with ALL and healthy controls were recruited and genotyped for genetic variants of TPMT and ITPA 94C>A. The relationship between genotypes and clinical outcomes was investigated.
  
  
  CONCLUSIONS
  Acute lymphoblastic leukaemia patients with allele ITPA 94A were more likely to develop fever and liver toxicity with 6-MP. The prevalence of TPMT variants was low and this makes it unlikely that testing for them would be useful in our populations. Only patients heterozygous for TPMT*3C were detected.
  
  
  CONCLUSIONS
  Our results suggest that ITPA 94C>A testing, but not TPMT testing, may help in minimizing the adverse effects of 6-MP in Malaysian patients. However, whether this is true in clinical practice requires a larger study and formal randomized controlled evaluation.
authors.affiliation: Pharmacogenomics Center (PROMISE), Faculty of Pharmacy, Universiti Teknologi MARA, Selangor, Malaysia.
authors.forename: W R
authors.initials: WR
authors.lastname: Wan Rosalina
authors.forename: L K
authors.initials: LK
authors.lastname: Teh
authors.forename: N
authors.initials: N
authors.lastname: Mohamad
authors.forename: A
authors.initials: A
authors.lastname: Nasir
authors.forename: R
authors.initials: R
authors.lastname: Yusoff
authors.forename: A A
authors.initials: AA
authors.lastname: Baba
authors.forename: M Z
authors.initials: MZ
authors.lastname: Salleh
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008296:Malaysia; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects* / Q000627:therapeutic use; D008780:Methyltransferases / Q000235:genetics*; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D011755:Pyrophosphatases / Q000235:genetics*; D055815:Young Adult; D000097630:Inosine Triphosphatase
chemical_list: D000964:Antimetabolites, Antineoplastic; D015122:Mercaptopurine; D008780:Methyltransferases; D011755:Pyrophosphatases; D000097630:Inosine Triphosphatase; C022745:thiopurine methyltransferase