TY - JOUR
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
PY - 2015/5/1
Y1 - 2015/5/1
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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U2 - 10.3109/10428194.2014.953154
DO - 10.3109/10428194.2014.953154
M3 - Article
C2 - 25115513
AN - SCOPUS:84932183754
SN - 1042-8194
VL - 56
SP - 1450
EP - 1459
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 5
ER -
