title: [Analysis of genetic polymorphisms of thiopurine S-methyltransferase (TPMT) in Mexican pediatric patients with cancer].
abstract: BACKGROUND
  Thiopurine S-Methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs, such as 6-mercaptopurine, 6-thioguanine and azathioprine, leading to their inactivation. Individuals who carry TPMT allele variants are more likely to experience life-threatening toxicity when these drugs are given at a standard dose. Wildtype phenotype TPMT*1 exhibits high level of catalytic activity, while all variants manifest with a decreased enzymatic activity. Ethnic-related differences in the distribution of TPMT variant alleles have been found. In Mexico, limited information is available; so far only two studies have been published and clear differences exist between them.
  
  
  METHODS
  Allelic variants and genotypes of the TPMT gene were determined in 240 Mexican children with leukemia and solid tumors using DNA extracted from peripheral blood. Polymorphisms G460A and A719G were identified by PCR-RFLP and G238C by the specific-allele PCR assay. The enzyme variants were detected by allelic discrimination.
  
  
  RESULTS
  Homozygous wild-type genotype TPMT*1/TPMT*1 was found in 173 patients (72.1%); 67 cases (27.9%) were heterozygous: 18 with genotype TPMT*1/TPMT*3B (7.5%), 17 TPMT*1/TPMT*3C (7.1%), 16 TPMT*1/TMPT*2 (6.7%), 14 TPMT*1/TPMT*3A (5.8%), and 2 (0.8%) were homozygous for two variants: TPMT*2/ TPMT*3B in both. The allele frequencies were TPMT*1 in 411 (85.62%), TPMT*3B in 20 (4.1%), TPMT*2 in 18 (3.75%), TPMT*3C in 17 (3.55%) and TPMT*3A in 14 (2.9%).
  
  
  CONCLUSIONS
  A high frequency and diversity of variant TPMT genotypes was found in this series with predominance of the TPMT*3B allele.
authors.affiliation: Departamento de Hemato-Oncología, Hospital Infantil de México Federico Gómez.
authors.forename: Silvia Selene
authors.initials: SS
authors.lastname: Moreno-Guerrero
authors.forename: Arturo
authors.initials: A
authors.lastname: Ramírez-Pacheco
authors.forename: Elsa María
authors.initials: EM
authors.lastname: Dorantes-Acosta
authors.forename: Aurora
authors.initials: A
authors.lastname: Medina-Sanson
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008800:Mexico; D009369:Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase