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

    Fingerprint

    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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    title = "Significance of 5,10-methylenetetrahydrofolate reductase gene variants in acute lymphoblastic leukemia in Indian population: An experimental, computational and meta-analysis",
    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.",
    author = "Ravishankara Bellampalli and Phani, {Nagaraja M.} and Bhat, {Kamalakshi G.} and Krishna Prasad and Nalini Bhaskaranand and Guruprasad, {Kanive P.} and Rai, {Padmalatha S.} and Kapaettu Satyamoorthy",
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    T1 - Significance of 5,10-methylenetetrahydrofolate reductase gene variants in acute lymphoblastic leukemia in Indian population

    T2 - An experimental, computational and meta-analysis

    AU - Bellampalli, Ravishankara

    AU - Phani, Nagaraja M.

    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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    N2 - 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.

    AB - 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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