title: [Phenotype and genotype of thiopurine methyltransferase in Chilean individuals].
abstract: BACKGROUND
  Thiopurines (azathioprine and 6-mercaptopurine) are highly effective medications but with potential adverse effects. Thiopurine methyltransferase (TMPT) is the key enzyme in their pharmacokinetics and is genetically regulated. A low activity of TPMT is associated with myelotoxicity. The genotype and enzyme activity can vary by ethnicity.
  
  
  OBJECTIVE
  To study the activity and genotype of TPMT in a group of Chilean subjects.
  
  
  METHODS
  In 200 healthy adult blood donors, TPMT activity was determined by high performance liquid chromatography (HPLC). Deficient, low, normal or high levels were defined when enzymatic activity was < 5, 6-24,25-55 and > 56 nmol/grHb/h, respectively. Genotyping of TPMT (*1, *2, *3A, *3B, *3C) was performed by PCR.
  
  
  RESULTS
  Seventy seven women (38.5%) and 123 men (61.5%), with an average age of 34.9 years were studied. Eighteen subjects (9%) had a low enzymatic activity, 178 (89%) had normal activity, 4 (2%) had high activity and no genotype deficient subjects were identified. The wild type genotype (*1) was found in 184 (92%) individuals and 16 (8%) were heterozygous for the variants: *2 (n = 2), *3A (n = 13) and *3C (n = 1). No homozygous subjects for these variants were identified. Wild type genotype had an increased enzymatic activity (40.8 ± 7.2 nmol/gHb/h) compared to heterozygous group (21.2 ± 3 nmol/ gHb/h; p < 0.001).
  
  
  CONCLUSIONS
  Less than 10% of a Chilean population sample has a low enzymatic activity or allelic variants in the TPMT gene, supporting the use of thiopurines according to international recommendations.
authors.affiliation: Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Chile.
authors.forename: Andrés
authors.initials: A
authors.lastname: Jorquera
authors.forename: Sandra
authors.initials: S
authors.lastname: Solari
authors.forename: Valeska
authors.initials: V
authors.lastname: Vollrath
authors.forename: Irene
authors.initials: I
authors.lastname: Guerra
authors.forename: José
authors.initials: J
authors.lastname: Chianale
authors.forename: Colomba
authors.initials: C
authors.lastname: Cofré
authors.forename: Alexis
authors.initials: A
authors.lastname: Kalergis
authors.forename: Patricio
authors.initials: P
authors.lastname: Ibáñez
authors.forename: Susan
authors.initials: S
authors.lastname: Bueno
authors.forename: Manuel
authors.initials: M
authors.lastname: Alvarez-Lobos
mesh_terms: D000328:Adult; D002677:Chile; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007199:Indians, South American / Q000235:genetics / Q000706:statistics & numerical data; D008297:Male; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase