Journal of Integrative Oncology

ISSN: 2329-6771

Open Access

Article in Press

Volume 10, Issue 1 (2021)

    Research Article Pages: 1 - 6

    MTHFR New Gene Variants Increase Risk Factor in Wilms' tumor and Prediction of 3D Structure Modulates Functional Activity During Drug-Protein Interaction

    Ajit Kumar Saxena1*, Vijayendra Kumar2, Aniket Kumar1 and Chandan Kumar Singh1

    Wilms’ tumor (WT) is an embryonic tumor of kidney that belongs to paediatric age group. The etiopathology is highly complex due to interaction between genetic
    and epigenetic factors. The genetic heterogeneity of methylene tetrahydrofolate reductase (MTHFR) gene polymorphism increase “risk factor” of the disease.
    The present study has been designed to identify new gene variants single nucleotide polymorphism (SNP) of MTHFR using Sanger’s sequencing and decode the
    nucleotide sequences into corresponding amino acids to understand the translational events. Further, allele refractive mutation system with polymerase chain
    reaction (ARMS- PCR) was also used to confirm mutations (frequency) in the cases of WT and compare with age matched controls. Present findings reveal
    that genetic heterozygosity was observed in 20% cases of WT by substitution of nucleotide cytosine in to thymidine (C→T) followed by change of amino acid
    alanine is replaced by valine due to missense mutation. DNA sequencing data varies in different cases of WT that includes - first case shows four new SNPs -1)
    nucleotide cytosine is substitute by thymidine (C→T) followed by change in amino acid alanine is replaced by valine, 2) thymidine change into adenine (T→A)
    results in isoleucine→asparagine, 3) cytosine is substitute by adenine (C→A) results in isoleucine →asparagine, and 4) thymidine is substitute by cytosine
    (T→C), where phenylalanine →serine. Similarly, Second and third case of WT again showing the missense mutation, where the nucleotide cytosine is substitute
    by thymidine (C→T) followed by alanine→valine and thymidine into adenine (T→A) followed by change in isoleucine→asparagine, respectively. Based on
    bioinformatics analysis, the 3D structure predicted that the mutation in MTHFR gene modulate the functional activity of ligand binding sites either with protein or
    methotrexate. Collective findings of PCR and DNA sequencing suggests that these new gene variants which has not been reported earlier might have interfere
    in folate - metabolism during DNA methylation and increase genetic susceptibility and “risk factor” in WT cases.

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