TY - JOUR
T1 - Involvement of MTHFR and TPMT genes in susceptibility to childhood acute lymphoblastic leukemia (ALL) in Mexicans
AU - Gutiérrez-Álvarez, Ossyneidee
AU - Lares-Asseff, Ismael
AU - Galaviz-Hernández, Carlos
AU - Reyes-Espinoza, Elio Aarón
AU - Almanza-Reyes, Horacio
AU - Sosa-Macías, Martha
AU - Chairez Hernández, Isaías
AU - Salas-Pacheco, José Manuel
AU - Bailón-Soto, Claudia E.
N1 - Publisher Copyright:
© 2016 by De Gruyter.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - MTHFR
KW - TPMT
KW - acute lymphoblastic leukemia
UR - http://www.scopus.com/inward/record.url?scp=84960879765&partnerID=8YFLogxK
U2 - 10.1515/dmpt-2015-0036
DO - 10.1515/dmpt-2015-0036
M3 - Artículo
C2 - 26845729
SN - 2363-8907
VL - 31
SP - 41
EP - 46
JO - Drug Metabolism and Personalized Therapy
JF - Drug Metabolism and Personalized Therapy
IS - 1
ER -