Genotipo y fenotipo de la enzima tiopurina metiltransferasa en población chilena / Phenotype and genotype of thiopurine methyltransferase in Chilean individuals
Rev. méd. Chile
; 140(7): 889-895, jul. 2012. ilus
Article
in Es
| LILACS
| ID: lil-656360
Responsible library:
CL1.1
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.Aim:
To study the activity and genotype of TPMT in a group of Chilean subjects. Material andMethods:
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.Key words
Full text:
1
Database:
LILACS
Main subject:
Methyltransferases
Limits:
Adult
/
Female
/
Humans
/
Male
Country/Region as subject:
America do sul
/
Chile
Language:
Es
Journal:
Rev. méd. Chile
Journal subject:
MEDICINA
Year:
2012
Type:
Article
/
Project document
Affiliation country:
Chile