title: Validation of a genotyping method for analysis of TPMT polymorphisms.
abstract: BACKGROUND
  Thiopurine methyltransferase (TPMT) catalyzes the methylation of thiopurine drugs such as azathioprine and 6-mercaptopurine. Several mutations in the TPMT gene correlate with low enzyme activity and adverse effects such as myelotoxicity. Hence, genotyping TPMT makes it possible to identify patients at high risk for drug toxicity.
  
  
  OBJECTIVE
  The aim of this study was to validate a TPMT genotyping method by comparing it with a conventional polymerase chain reaction (PCR) approach.
  
  
  METHODS
  LightSNiP is a real-time PCR method for the detection of TPMT*2, *3B, and *3C without a sequencing step. We evaluated the frequencies of 3 TPMT alleles in 111 white adult patients by comparing genotyping by LightSNiP with conventional PCR (sequencing).
  
  
  RESULTS
  No differences were observed between conventional genotyping with sequencing and LightSNiP for *2, *3B, and *3C, suggesting the validity of this method.
  
  
  CONCLUSIONS
  Compared with the conventional PCR sequencing method, the data suggest that LightSNiP correctly detected the TPMT *2, *3B, and *3C in this select population.
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, UAM, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Román
authors.forename: Teresa
authors.initials: T
authors.lastname: Cabaleiro
authors.forename: Dolores
authors.initials: D
authors.lastname: Ochoa
authors.forename: Jesús
authors.initials: J
authors.lastname: Novalbos
authors.forename: María
authors.initials: M
authors.lastname: Chaparro
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
authors.forename: Francisco
authors.initials: F
authors.lastname: Abad-Santos
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D005838:Genotype; D006801:Humans; D008780:Methyltransferases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: D017931:DNA Primers; D008780:Methyltransferases; C022745:thiopurine methyltransferase