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Involvement of MTHFR and TPMT genes in susceptibility to childhood acute lymphoblastic leukemia (ALL) in Mexicans

  • Ossyneidee Gutiérrez-Álvarez , Ismael Lares-Asseff EMAIL logo , Carlos Galaviz-Hernández , Elio-Aarón Reyes-Espinoza , Horacio Almanza-Reyes , Martha Sosa-Macías , Isaías Chairez Hernández , José-Manuel Salas-Pacheco and Claudia E. Bailón-Soto
Published/Copyright: February 4, 2016

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.


Corresponding author: Ismael Lares-Asseff, Instituto Politécnico Nacional (IPN), Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional (CIIDIR), Unidad Durango, Sigma #119 Fracc, 20 de Noviembre II, Durango, Dgo., México, Phone: +52 618 8142091, Fax: +52 618 8144550, E-mail:

Acknowledgments

We are grateful to Jehová-Nissi who made the study possible. We are grateful to Maria Cristina Venzor Sanchez from El Centro Estatal de Cancerología del Estado de Durango for her assistance with sample collection. Additionally, we offer our gratitude to CONACYT for the postgraduate scholarship provided to O.G.-A. at CIIDIR-Durango IPN.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2015-9-22
Accepted: 2016-1-4
Published Online: 2016-2-4
Published in Print: 2016-3-1

©2016 by De Gruyter

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