title: Thiopurine S-methyltransferase (TPMT) genetic polymorphisms in Mexican newborns.
abstract: BACKGROUND
  Thiopurine S-methyltransferase (TPMT) is involved in the toxicity and therapeutic efficacy of thiopurine drugs, and its gene exhibits genetic polymorphisms that differ across diverse populations. Four TPMT polymorphisms (TPMT*2, *3A, *3B and *3C) account for 80-95% of alleles that cause reduced enzyme activity. To date, only a single study in the Mexican population involving 108 individuals has been performed, but the regional and ethnic origin of this population was not described. Accordingly, information about the TPMT polymorphism in the Mexican population is limited.
  
  
  OBJECTIVE
  To determine the TPMT allele and genotype frequencies in a sample of newborns from Mexico City.
  
  
  METHODS
  Three hundred and sixty DNA samples from unrelated, anonymous individuals were obtained from dried blood spots collected on filter paper as part of the Newborn Screening National Program. Allele-specific polymerase chain reaction for the TPMT*2 allele and PCR restriction fragment length polymorphism for TPMT*3A, TPMT*3B, TPMT*3C alleles were used to determine the respective allelic and genotypic frequencies.
  
  
  CONCLUSIONS
  Of 720 TPMT alleles analysed, 49 (6.81%) were deficiency alleles. The most common deficiency allele was TPMT*3A (5.69%), followed by TPMT*3C (0.56%), TPMT*3B (0.28%) and TPMT*2 (0.28%). Fourty-five newborns were heterozygous for one mutant allele (12.5%) and two showed a genotype with two deficiency alleles (0.56%). Despite its unique ethnic composition, our Mexican population exhibited variant allele frequencies that were similar to some Caucasian populations.
  
  
  CONCLUSIONS
  Our data suggest that approximately 1 in 180 persons born in Mexico City might have low or undetectable TPMT enzyme activity, a frequency that, overall, is somewhat higher than that reported for Caucasian populations generally (1 in 300).
authors.affiliation: Molecular Biology Laboratory, Genetics Department, Instituto Nacional de Pediatría, DF, México. agonzalezdelangel@salud.gob.mx
authors.forename: A
authors.initials: A
authors.lastname: González-Del Angel
authors.forename: C
authors.initials: C
authors.lastname: Bermúdez-López
authors.forename: M A
authors.initials: MA
authors.lastname: Alcántara-Ortigoza
authors.forename: M
authors.initials: M
authors.lastname: Vela-Amieva
authors.forename: R A
authors.initials: RA
authors.lastname: Castillo-Cruz
authors.forename: V
authors.initials: V
authors.lastname: Martínez
authors.forename: L
authors.initials: L
authors.lastname: Torres-Espíndola
mesh_terms: D002851:Chromatography, High Pressure Liquid; D005787:Gene Frequency; D006801:Humans; D007231:Infant, Newborn; D008780:Methyltransferases / Q000235:genetics*; D008800:Mexico; D011110:Polymorphism, Genetic
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase