Methylenetetrahydrofolate reductase C677T genetic polymorphisms and risk of leukaemia among the North Indian population

Hussain, Syed Rizwan; Naqvi, Hena; Raza, Syed Tasleem; Ahmed, Faisal; Babu, Sunil G.; Kumar, Ashutosh; Zaidi, Zeashan Haider; Mahdi, Farzana

doi:10.1016/j.canep.2012.02.008

Cited by 21 publications

(16 citation statements)

References 27 publications

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“…However, some studies have suggested that 1298AC variants significantly decreased the risks of acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) compared with 1298AA [8,11]. Results have been conflicting, with some studies reporting no effect for MTHFR C677T [8,11,12], and others yielding evidence of an effect at least for MTHFR 677TT [9,10]. A meta-analysis between AML and the MTHFR polymorphisms from nine individual case-control studies reported that the OR for the 1298AC genotype was 0.98 (95% CI = 0.85-1.13) compared with the 1298AA genotype, and that for the 677TT genotype was 1.04 (95% CI = 0.87-1.25) compared with the 677CC genotype [17].…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) are associated with susceptibility to adult acute myeloid leukemia in a Chinese population

Huang

Deng

Peng

et al. 2015

Cancer Epidemiology

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Section: Discussionmentioning

confidence: 92%

“…It is therefore probable that decreased catalytic activity and subsequent availability of 5,10-MeTHF and SAM are related to AML. Nevertheless, the results of previous studies have been inconsistent [8][9][10], and the combined effects of C677T and A1298C have rarely been evaluated [11,12].…”

Section: Introductionmentioning

confidence: 90%

Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) are associated with susceptibility to adult acute myeloid leukemia in a Chinese population

Huang

Deng

Peng

et al. 2015

Cancer Epidemiology

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“…Six studies were excluded (two studies [26], [27] were conference articles, and two [28], [29] with patients were about therapy-related AML, one [11] was review article, and one [30] was supplementary material). Finally, 13 studies [7], [14]–[25] were included in this meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

“…To date, several studies have investigated the association between MTHFR polymorphisms and AML risk [7], [11], [14]–[30], but results from those studies remain inconsistent. Therefore, we conducted a meta-analysis of previously published studies to assess the relationship between the MTHFR polymorphisms and AML risk.…”

Section: Introductionmentioning

confidence: 99%

Association between MTHFR Polymorphisms and Acute Myeloid Leukemia Risk: A Meta-Analysis

Qin

Zhang

et al. 2014

PLoS ONE

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Previous observational studies investigating the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and acute myeloid leukemia risk (AML) have yielded inconsistent results. The aim of this study is to derive a more precise estimation of the association between MTHFR (C677T and A1298C) polymorphisms and acute myeloid leukemia risk. PubMed and Embase databases were systematically searched to identify relevant studies from their inception to August 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were the metric of choice. Thirteen studies were selected for C677T polymorphism (1838 cases and 5318 controls) and 9 studies (1335 patients and 4295 controls) for A1298C polymorphism. Overall, pooled results showed that C677T polymorphism was not significant associated with AML risk(OR, 0.98–1.04; 95% CI, 0.86–0.92 to 1.09–1.25). Similar results were observed for the A1298C polymorphism and in subgroup analysis. All comparisons revealed no substantial heterogeneity nor did we detect evidence of publication bias. In summary, this meta-analysis provides evidence that MTHFR polymorphisms were not associated with AML risk. Further investigations are needed to offer better insight into the role of these polymorphisms in AML carcinogenesis.

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“…Polymorphisms in genes involved in methylation pathway were not found to influence the risk of ALL in Indian population [10][11][12][13][14]. Thus, exploring the variants in DNA synthesis pathway enzymes such as dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS) may provide insights in to the susceptibility to ALL.…”

Section: Introductionmentioning

confidence: 99%

Genotype Distribution of Dihydrofolatereductase Variants and their Role in Disease Susceptibility to Acute Lymphoblastic Leukemia in Indian Population: An Experimental and Computational Analysis

Kodidela¹,

Pradhan²

2016

J Leuk

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Objectives: To establish the allele and genotype frequencies of dihydrofolate reductase (DHFR) -317A>G and -680C>A variants in Indian population, to find the association of these variants with the risk of acute lymphoblastic leukemia (ALL) and to analyze the effects of non-synonymous SNPs (nsSNPs) and 3'untranslated region (3'UTR) variants of DHFR gene on its structure and function using in-silico tools.Methods: A total of 235 unrelated healthy volunteers (controls) and 127 ALL patients (cases) were recruited for the study. DNA was extracted from peripheral leucocytes. Genotyping of DHFR polymorphisms was done by realtime PCR. We investigated the deleterious effect of nsSNPs and variants in 3'UTR of DHFR gene through computational platforms. Results:In the present study, the frequency of DHFR -317G and -680 A alleles was found to be 33.3% and 59.8% respectively. The studied DHFR variants (rs408626 and rs442767) did not confer a significant risk for ALL. Insilico analysis revealed that three nsSNPs potentially affect the structure, function and activity of the DHFR protein.Four microRNA binding sites were found to be highly affected due to 3'UTR SNPs. Further, docking simulation suggested that the order of binding affinity of methotrexate towards native and all three mutant forms of DHFR is D153V (rs121913223)>native>G18R (rs61736208)>D187Y (rs200904105). Conclusion:This is the first study to report the normative genotype distribution of DHFR variants in Indian population and also to report that DHFR (-317A>G and -680C>A) variants do not confer a potential risk for development of ALL. Inter-ethnic differences exist in the distribution of DHFR variant genotypes, and this can lead to variability in therapeutic response to DHFR substrates. Protein sequence analysis revealed rs200904105 influences the phosphorylation process (post-translational modification) of DHFR and docking simulation suggested methotrexate to have a higher affinity towards rs121913223 mutant form. Therefore, studies are warranted to explore the clinical impact of these variants in the Indian population.

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Methylenetetrahydrofolate reductase C677T genetic polymorphisms and risk of leukaemia among the North Indian population

Cited by 21 publications

References 27 publications

Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) are associated with susceptibility to adult acute myeloid leukemia in a Chinese population

Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) are associated with susceptibility to adult acute myeloid leukemia in a Chinese population

Association between MTHFR Polymorphisms and Acute Myeloid Leukemia Risk: A Meta-Analysis

Genotype Distribution of Dihydrofolatereductase Variants and their Role in Disease Susceptibility to Acute Lymphoblastic Leukemia in Indian Population: An Experimental and Computational Analysis

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