Acute lymphoblastic leukemia and genetic variations in BHMT gene: Case-control study and computational characterization

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. Insilico 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 30-UTR (rs59109725, rs116634518 and rs138578732) alter the miRNAbinding site, and 11 CNVs are present in the BHMT gene. As consequence of BHMT (rs3733890) polymorphism the free energy changes from