Acute lymphoblastic leukemia and genetic variations in BHMT gene

Case-control study and computational characterization

Ravishankara Bellampalli, Manik Vohra, Kashish Sharma, Nalini Bhaskaranand, Kamalakshi G. Bhat, Krishna Prasad, Anu R. Sharma, Kapaettu Satyamoorthy, Padmalatha S. Rai

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

BACKGROUND: Remethylation of homocysteine is catalyzed by B12 dependent methionine synthase (MTR) in all types of cells and by B12 non-dependent betaine homocysteine methyltransferase (BHMT) in liver and kidney cells. Of many etiologies of cancer, an unexplored area is the variations of genes implicated in methylation reaction. OBJECTIVE: The study evaluated the association of BHMT (rs3733890) with acute lymphoblastic leukemia (ALL), followed by in-silico characterization of variations in BHMT gene. METHODS: BHMT [rs3733890; c.742G > A, which substitutes an arginine by a glutamine at codon 239 (R239Q)] was screened by Tetra-primer Amplification Refractory Mutation System PCR (T-ARMS-PCR) and confirmed using DNA sequencing. In-silico analysis was conducted using bioinformatics tools. RESULTS: BHMT (rs3733890) showed an insignificant association with both childhood and adult ALL. Bioinformatics analysis showed that 18 nsSNPs are deleterious, 3 SNPs in 3′-UTR (rs59109725, rs116634518 and rs138578732) alter the miRNA-binding site, and 11 CNVs are present in the BHMT gene. As consequence of BHMT (rs3733890) polymorphism the free energy changes from -101210.1 kJ/mol to -200021.8 kJ/mol. CONCLUSIONS: BHMT (rs3733890) polymorphism showed no association with ALL. Hence this investigation needs further evaluation in larger sample size and effect of other SNPs, CNVs and miRNA's is required to elucidate the role of BHMT gene in ALL development.

Original languageEnglish
Pages (from-to)393-401
Number of pages9
JournalCancer Biomarkers
Volume19
Issue number4
DOIs
Publication statusPublished - 2017

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Betaine-Homocysteine S-Methyltransferase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Case-Control Studies
Genes
Computational Biology
MicroRNAs
Computer Simulation
Single Nucleotide Polymorphism
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
3' Untranslated Regions
Homocysteine
Glutamine
DNA Sequence Analysis
Codon
Sample Size
Methylation
Arginine

All Science Journal Classification (ASJC) codes

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Bellampalli, Ravishankara ; Vohra, Manik ; Sharma, Kashish ; Bhaskaranand, Nalini ; Bhat, Kamalakshi G. ; Prasad, Krishna ; Sharma, Anu R. ; Satyamoorthy, Kapaettu ; Rai, Padmalatha S. / Acute lymphoblastic leukemia and genetic variations in BHMT gene : Case-control study and computational characterization. In: Cancer Biomarkers. 2017 ; Vol. 19, No. 4. pp. 393-401.
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title = "Acute lymphoblastic leukemia and genetic variations in BHMT gene: Case-control study and computational characterization",
abstract = "BACKGROUND: Remethylation of homocysteine is catalyzed by B12 dependent methionine synthase (MTR) in all types of cells and by B12 non-dependent betaine homocysteine methyltransferase (BHMT) in liver and kidney cells. Of many etiologies of cancer, an unexplored area is the variations of genes implicated in methylation reaction. OBJECTIVE: The study evaluated the association of BHMT (rs3733890) with acute lymphoblastic leukemia (ALL), followed by in-silico characterization of variations in BHMT gene. METHODS: BHMT [rs3733890; c.742G > A, which substitutes an arginine by a glutamine at codon 239 (R239Q)] was screened by Tetra-primer Amplification Refractory Mutation System PCR (T-ARMS-PCR) and confirmed using DNA sequencing. In-silico analysis was conducted using bioinformatics tools. RESULTS: BHMT (rs3733890) showed an insignificant association with both childhood and adult ALL. Bioinformatics analysis showed that 18 nsSNPs are deleterious, 3 SNPs in 3′-UTR (rs59109725, rs116634518 and rs138578732) alter the miRNA-binding site, and 11 CNVs are present in the BHMT gene. As consequence of BHMT (rs3733890) polymorphism the free energy changes from -101210.1 kJ/mol to -200021.8 kJ/mol. CONCLUSIONS: BHMT (rs3733890) polymorphism showed no association with ALL. Hence this investigation needs further evaluation in larger sample size and effect of other SNPs, CNVs and miRNA's is required to elucidate the role of BHMT gene in ALL development.",
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Acute lymphoblastic leukemia and genetic variations in BHMT gene : Case-control study and computational characterization. / Bellampalli, Ravishankara; Vohra, Manik; Sharma, Kashish; Bhaskaranand, Nalini; Bhat, Kamalakshi G.; Prasad, Krishna; Sharma, Anu R.; Satyamoorthy, Kapaettu; Rai, Padmalatha S.

In: Cancer Biomarkers, Vol. 19, No. 4, 2017, p. 393-401.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Acute lymphoblastic leukemia and genetic variations in BHMT gene

T2 - Case-control study and computational characterization

AU - Bellampalli, Ravishankara

AU - Vohra, Manik

AU - Sharma, Kashish

AU - Bhaskaranand, Nalini

AU - Bhat, Kamalakshi G.

AU - Prasad, Krishna

AU - Sharma, Anu R.

AU - Satyamoorthy, Kapaettu

AU - Rai, Padmalatha S.

PY - 2017

Y1 - 2017

N2 - BACKGROUND: Remethylation of homocysteine is catalyzed by B12 dependent methionine synthase (MTR) in all types of cells and by B12 non-dependent betaine homocysteine methyltransferase (BHMT) in liver and kidney cells. Of many etiologies of cancer, an unexplored area is the variations of genes implicated in methylation reaction. OBJECTIVE: The study evaluated the association of BHMT (rs3733890) with acute lymphoblastic leukemia (ALL), followed by in-silico characterization of variations in BHMT gene. METHODS: BHMT [rs3733890; c.742G > A, which substitutes an arginine by a glutamine at codon 239 (R239Q)] was screened by Tetra-primer Amplification Refractory Mutation System PCR (T-ARMS-PCR) and confirmed using DNA sequencing. In-silico analysis was conducted using bioinformatics tools. RESULTS: BHMT (rs3733890) showed an insignificant association with both childhood and adult ALL. Bioinformatics analysis showed that 18 nsSNPs are deleterious, 3 SNPs in 3′-UTR (rs59109725, rs116634518 and rs138578732) alter the miRNA-binding site, and 11 CNVs are present in the BHMT gene. As consequence of BHMT (rs3733890) polymorphism the free energy changes from -101210.1 kJ/mol to -200021.8 kJ/mol. CONCLUSIONS: BHMT (rs3733890) polymorphism showed no association with ALL. Hence this investigation needs further evaluation in larger sample size and effect of other SNPs, CNVs and miRNA's is required to elucidate the role of BHMT gene in ALL development.

AB - BACKGROUND: Remethylation of homocysteine is catalyzed by B12 dependent methionine synthase (MTR) in all types of cells and by B12 non-dependent betaine homocysteine methyltransferase (BHMT) in liver and kidney cells. Of many etiologies of cancer, an unexplored area is the variations of genes implicated in methylation reaction. OBJECTIVE: The study evaluated the association of BHMT (rs3733890) with acute lymphoblastic leukemia (ALL), followed by in-silico characterization of variations in BHMT gene. METHODS: BHMT [rs3733890; c.742G > A, which substitutes an arginine by a glutamine at codon 239 (R239Q)] was screened by Tetra-primer Amplification Refractory Mutation System PCR (T-ARMS-PCR) and confirmed using DNA sequencing. In-silico analysis was conducted using bioinformatics tools. RESULTS: BHMT (rs3733890) showed an insignificant association with both childhood and adult ALL. Bioinformatics analysis showed that 18 nsSNPs are deleterious, 3 SNPs in 3′-UTR (rs59109725, rs116634518 and rs138578732) alter the miRNA-binding site, and 11 CNVs are present in the BHMT gene. As consequence of BHMT (rs3733890) polymorphism the free energy changes from -101210.1 kJ/mol to -200021.8 kJ/mol. CONCLUSIONS: BHMT (rs3733890) polymorphism showed no association with ALL. Hence this investigation needs further evaluation in larger sample size and effect of other SNPs, CNVs and miRNA's is required to elucidate the role of BHMT gene in ALL development.

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