Significance of 5,10-methylenetetrahydrofolate reductase gene variants in acute lymphoblastic leukemia in Indian population: An experimental, computational and meta-analysis

Ravishankara Bellampalli, Nagaraja M. Phani, Kamalakshi G. Bhat, Krishna Prasad, Nalini Bhaskaranand, Kanive P. Guruprasad, Padmalatha S. Rai, Kapaettu Satyamoorthy

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Abstract

Acute lymphoblastic leukemia (ALL) arises due to several genetic alterations in progenitor cells, and methotrexate is frequently used as part of the treatment regimen. Although there is evidence for an effect of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) C677T and A1298C variations on drug response in ALL, its risk association for ALL is still unresolved. In a case-control study of 203 patients with ALL and 246 controls and meta-analysis in the Indian population, we showed an insignificant association of MTHFR C677T and A1298C genotypes with childhood and adult ALL. Comprehensive in silico characterization of non-synonymous single nucleotide polymorphisms (nsSNPs) and SNPs of the 3′ untranslated region (UTR) revealed nine nsSNPs as deleterious, and three SNPs in the 3′UTR could possibly alter the binding of miRNAs. The study revealed that several overlooked SNPs may contribute to the risk of ALL susceptibility and further studies of these SNPs with functional characterization in a large sample size are required to understand the significant role of MTHFR in ALL development.

Original languageEnglish
Pages (from-to)1450-1459
Number of pages10
JournalLeukemia and Lymphoma
Volume56
Issue number5
DOIs
Publication statusPublished - 01-05-2015

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Methylenetetrahydrofolate Reductase (NADPH2)
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Meta-Analysis
Single Nucleotide Polymorphism
Population
Genes
3' Untranslated Regions
MicroRNAs
Methotrexate
Computer Simulation
Sample Size
Case-Control Studies
Stem Cells
Genotype

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

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abstract = "Acute lymphoblastic leukemia (ALL) arises due to several genetic alterations in progenitor cells, and methotrexate is frequently used as part of the treatment regimen. Although there is evidence for an effect of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) C677T and A1298C variations on drug response in ALL, its risk association for ALL is still unresolved. In a case-control study of 203 patients with ALL and 246 controls and meta-analysis in the Indian population, we showed an insignificant association of MTHFR C677T and A1298C genotypes with childhood and adult ALL. Comprehensive in silico characterization of non-synonymous single nucleotide polymorphisms (nsSNPs) and SNPs of the 3′ untranslated region (UTR) revealed nine nsSNPs as deleterious, and three SNPs in the 3′UTR could possibly alter the binding of miRNAs. The study revealed that several overlooked SNPs may contribute to the risk of ALL susceptibility and further studies of these SNPs with functional characterization in a large sample size are required to understand the significant role of MTHFR in ALL development.",
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AU - Bhat, Kamalakshi G.

AU - Prasad, Krishna

AU - Bhaskaranand, Nalini

AU - Guruprasad, Kanive P.

AU - Rai, Padmalatha S.

AU - Satyamoorthy, Kapaettu

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