ASSOCIATION OF MTHFR POLYMORPHISMS AND CHROMOSOMAL
ABNORMALITIES IN ACUTE LYMPHOBLASTIC LEUKEMIA
Rim Frikha
Medical Genetic department, Sfax, Tunisia
Background: Polymorphisms in genes involved in folate metabolism are commonly associated
with defects in folate-dependent homocysteine metabolism, which can result in DNA
hypomethylation and chromosome nondisjunction. Genetic variation in MTHFR gene (the
677C>T and 1298A>C) has been proposed as risk factor of chromosome abnormalities in
several diseases but still under debate in acute lymphoblastic leukemia patients (ALL) 1, 2.
Objective: In this study we aimed to determine the correlation of the 677C>T and 1298A>C
MTHFR polymorphisms with the presence of cytogenetic abnormalities among Tunisian
childhood ALL.
Methods: This study was conducted in 41 children with ALL treated with the EORTC 58951.
Clinical and biological data were recorded. Genomic DNA was extracted from whole venous
blood and genotyping were carried out with restriction fragment length polymorphism
(RFLP)3.
Results: The allelic frequency of MTHFR C677T and A1298C was 6.3% and 37.5% respectively.
The distribution of the 677C>T genotype increased in the patients with abnormal
chromosomes (RR=3 p=0.182). Yet, the frequency of C allele (A1298) in the patients with
normal karyotype was greater than those with abnormal chromosome (p=0.182).
Conclusion: Our preliminary results in a small number of patients with cytogenetic studies
require confirmation and extension in larger studies. Although chromosomal rearrangement
has been recognized as a major cause of lymphoid malignancies, it is likely that other genes
and environmental factors interfere with individual's susceptibility to these chromosomal
aberrations, including MTHFR polymorphisms.
References
1. Sinthuwiwat, T., et al., Association of MTHFR polymorphisms and chromosomal
abnormalities in leukemia. Dis Markers, 2012. 32(2): p. 115-21.
2. Gallegos-Arreola, M.P., et al., The MTHFR polymorphism C677T in adult patients with
acute lymphoblastic leukemia is associated with an increased prevalence of
cytogenetic abnormalities. Blood Cells Mol Dis, 2008. 40(2): p. 244-5.
3. Frikha, R., et al., A duplex polymerase chain reaction-restriction fragment length
polymorphism for rapid screening of methylenetetrahydrofolate reductase gene
variants: Genotyping in acute leukemia. J Clin Lab Anal, 2018. 32(1).
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