title: Involvement of MTHFR and TPMT genes in susceptibility to childhood acute lymphoblastic leukemia (ALL) in Mexicans.
abstract: BACKGROUND
  Folate metabolism plays an essential role in the processes of DNA synthesis and methylation. Deviations in the folate flux resulting from single-nucleotide polymorphisms in genes encoding folate-dependent enzymes may affect the susceptibility to leukemia. This case-control study aimed to assess associations among MTHFR (C677T, A1298C) and TPMT (*2, *3A) mutations as well as to evaluate the synergistic effects of combined genotypes for both genes. Therefore, these genetic variants may lead to childhood acute lymphoblastic leukemia (ALL) susceptibility, in a Mexican population study.
  
  
  METHODS
  DNA samples obtained from 70 children with ALL and 152 age-matched controls (range, 1-15 years) were analyzed by real-time reverse transcription polymerase chain reaction (RT-qPCR) to detect MTHFR C677T and A1298C and TPMT*2 and TPMT*3A genotypes.
  
  
  RESULTS
  The frequency of the MTHFR A1298C CC genotype was statistically significant (odds ratio [OR], 6.48; 95% 95% confidence intervals [CI], 1.26-33.2; p=0.025). In addition, the combined 677CC+1298AC genotype exhibited a statistically significant result (OR, 0.23; 95% CI, 0.06-0.82; p=0.023). No significant results were obtained from the MTHFR (C677T CT, C677T TT) or TPMT (*2, *3A) genotypes. More importantly, no association between the synergistic effects of either gene (MTHFR and/or TPMT) and susceptibility to ALL was found.
  
  
  CONCLUSIONS
  The MTHFR A1298C CC genotype was associated with an increased risk of developing childhood ALL. However, a decreased risk to ALL with the combination of MTHFR 677CC+1298AC genotypes was found.
authors: Ossyneidee
authors: O
authors: Gutiérrez-Álvarez
authors: Ismael
authors: I
authors: Lares-Asseff
authors: Carlos
authors: C
authors: Galaviz-Hernández
authors: Elio-Aarón
authors: EA
authors: Reyes-Espinoza
authors: Horacio
authors: H
authors: Almanza-Reyes
authors: Martha
authors: M
authors: Sosa-Macías
authors: Isaías
authors: I
authors: Chairez Hernández
authors: José-Manuel
authors: JM
authors: Salas-Pacheco
authors: Claudia E
authors: CE
authors: Bailón-Soto
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008780:Methyltransferases / Q000235:genetics*; D008800:Mexico; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008780:Methyltransferases; C022745:thiopurine methyltransferase