Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena

Andrés Jorquera; Sandra Solari; Valeska Vollrath; Irene Guerra; José Chianale; Colomba Cofré; Alexis M. Kalergis; Patricio Ibáñez; Susan Bueno; Manuel Álvarez-Lobos

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Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena

Andrés Jorquera ^[1] ; Sandra Solari ^[1] ; Valeska Vollrath ^[1] ; Irene Guerra ^[1] ; José Chianale ^[1] ; Colomba Cofré ^[1] ; Alexis Kalergis ^[1] ; Patricio Ibáñez ^[1] ; Susan Bueno ^[1] ; Manuel Álvarez-Lobos ^[1]
1. [1] Pontificia Universidad Católica de Chile
  
  Pontificia Universidad Católica de Chile
  
  Santiago, Chile
Localización: Revista Médica de Chile, ISSN-e 0034-9887, Vol. 140, Nº. 7, 2012, págs. 889-895
Idioma: español
Títulos paralelos:
- Phenotype and genotype of thiopurine methyltransferase in Chilean individuals
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Resumen
- 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. Aim: To study the activity and genotype of TPMT in a group of Chilean subjects. Material and 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.