Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jorquera,Andrés, Solari,Sandra, Vollrath,Valeska, Guerra,Irene, Chianale,José, Cofré,Colomba, Kalergis,Alexis, Ibáñez,Patricio, Bueno,Susan, Álvarez-Lobos,Manuel
Lenguaje:	Spanish / Castilian
Publicado:	Sociedad Médica de Santiago 2012
Materias:	Drug hypersensitivity Chile Gentype TPMT deficiency Phenotype
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872012000700009
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:scielo:S0034-98872012000700009
record_format	dspace
spelling	oai:scielo:S0034-988720120007000092012-10-22Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilenaJorquera,AndrésSolari,SandraVollrath,ValeskaGuerra,IreneChianale,JoséCofré,ColombaKalergis,AlexisIbáñez,PatricioBueno,SusanÁlvarez-Lobos,Manuel Drug hypersensitivity Chile Gentype TPMT deficiency Phenotype 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.info:eu-repo/semantics/openAccessSociedad Médica de SantiagoRevista médica de Chile v.140 n.7 20122012-07-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872012000700009es10.4067/S0034-98872012000700009
institution	Scielo Chile
collection	Scielo Chile
language	Spanish / Castilian
topic	Drug hypersensitivity Chile Gentype TPMT deficiency Phenotype
spellingShingle	Drug hypersensitivity Chile Gentype TPMT deficiency Phenotype Jorquera,Andrés Solari,Sandra Vollrath,Valeska Guerra,Irene Chianale,José Cofré,Colomba Kalergis,Alexis Ibáñez,Patricio Bueno,Susan Álvarez-Lobos,Manuel Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena
description	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.
author	Jorquera,Andrés Solari,Sandra Vollrath,Valeska Guerra,Irene Chianale,José Cofré,Colomba Kalergis,Alexis Ibáñez,Patricio Bueno,Susan Álvarez-Lobos,Manuel
author_facet	Jorquera,Andrés Solari,Sandra Vollrath,Valeska Guerra,Irene Chianale,José Cofré,Colomba Kalergis,Alexis Ibáñez,Patricio Bueno,Susan Álvarez-Lobos,Manuel
author_sort	Jorquera,Andrés
title	Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena
title_short	Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena
title_full	Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena
title_fullStr	Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena
title_full_unstemmed	Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena
title_sort	genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena
publisher	Sociedad Médica de Santiago
publishDate	2012
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0034-98872012000700009
work_keys_str_mv	AT jorqueraandres genotipoyfenotipodelaenzimatiopurinametiltransferasaenpoblacionchilena AT solarisandra genotipoyfenotipodelaenzimatiopurinametiltransferasaenpoblacionchilena AT vollrathvaleska genotipoyfenotipodelaenzimatiopurinametiltransferasaenpoblacionchilena AT guerrairene genotipoyfenotipodelaenzimatiopurinametiltransferasaenpoblacionchilena AT chianalejose genotipoyfenotipodelaenzimatiopurinametiltransferasaenpoblacionchilena AT cofrecolomba genotipoyfenotipodelaenzimatiopurinametiltransferasaenpoblacionchilena AT kalergisalexis genotipoyfenotipodelaenzimatiopurinametiltransferasaenpoblacionchilena AT ibanezpatricio genotipoyfenotipodelaenzimatiopurinametiltransferasaenpoblacionchilena AT buenosusan genotipoyfenotipodelaenzimatiopurinametiltransferasaenpoblacionchilena AT alvarezlobosmanuel genotipoyfenotipodelaenzimatiopurinametiltransferasaenpoblacionchilena
_version_	1718436637689511936

Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena

Ejemplares similares