ArticleProceedings of the National Academy of Sciences of the United States of America2002
A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 319 papers, 11 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
319 citing papers in PubMed, 11 syntheses or guidelines pooled it, 928 citations in OpenAlex.
- Association of MTHFR C677T polymorphism and type 2 diabetes mellitus (T2DM) susceptibility.Molecular genetics & genomic medicine · 2019Pooled it
- Methylenetetrahydrofolate reductase A1298C genetic variant& risk of schizophrenia: A meta-analysis.The Indian journal of medical research · 2017Pooled it
- Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes.PloS one · 2017Pooled it
- Pooled it
- Association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma susceptibility: evidence from a meta-analysis.Scientific reports · 2014Pooled it
- Meta-analysis of Methylenetetrahydrofolate reductase maternal gene in Down syndrome: increased susceptibility in women carriers of the MTHFR 677T allele.Molecular biology reports · 2014Pooled it
- Folate intake and MTHFR polymorphism C677T is not associated with ovarian cancer risk: evidence from the meta-analysis.Molecular biology reports · 2013Pooled it
- Association of methylenetetrahydrofolate reductase gene 677C > T polymorphism and Down syndrome.Molecular biology reports · 2013Pooled it
- Genetic variants in the folate pathway and the risk of neural tube defects: a meta-analysis of the published literature.PloS one · 2013Pooled it
- The association between MTHFR gene polymorphisms and hepatocellular carcinoma risk: a meta-analysis.PloS one · 2013Pooled it
- Pooled it
- The role of the folate pathway in pancreatic cancer risk.PloS one · 2018Trial
- Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2017Trial
- Effects of Italian Mediterranean organic diet vs. low-protein diet in nephropathic patients according to MTHFR genotypes.Journal of nephrology · 2014Trial
- Neither folic acid supplementation nor pregnancy affects the distribution of folate forms in the red blood cells of women.The Journal of nutrition · 2014Trial
- The association between MTHFR 677C>T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia.The American journal of clinical nutrition · 2013Trial
- Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia.JAMA psychiatry · 2013Trial
- Review
- Associations between Red Blood Cell Folate Forms and Demographic, Physiologic, and Lifestyle Factors in the United States Population: Cross-Sectional Data from the National Health and Nutrition Examination Survey August 2021-August 2023.Current developments in nutrition · 2026Article
- Integrating whole-genome bisulfite sequencing and TCGA data reveals methylation patterns associated with the MTHFR 677 C > T Variant.Scientific reports · 2026Article
259 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation, an essential epigenetic feature of DNA that modulates gene expression and genomic integrity, is catalyzed by methyltransferases that use the universal methyl donor S-adenosyl-l-methionine. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate (5-methylTHF), the methyl donor for synthesis of methionine from homocysteine and precursor of S-adenosyl-l-methionine. In the present study we sought to determine the effect of folate status on genomic DNA methylation with an emphasis on the interaction with the common C677T mutation in the MTHFR gene. A liquid chromatography/MS method for the analysis of nucleotide bases was used to assess genomic DNA methylation in peripheral blood mononuclear cell DNA from 105 subjects homozygous for this mutation (T/T) and 187 homozygous for the wild-type (C/C) MTHFR genotype. The results show that genomic DNA methylation directly correlates with folate status and inversely with plasma homocysteine (tHcy) levels (P < 0.01). T/T genotypes had a diminished level of DNA methylation compared with those with the C/C wild-type (32.23 vs.62.24 ng 5-methylcytosine/microg DNA, P < 0.0001). When analyzed according to folate status, however, only the T/T subjects with low levels of folate accounted for the diminished DNA methylation (P < 0.0001). Moreover, in T/T subjects DNA methylation status correlated with the methylated proportion of red blood cell folate and was inversely related to the formylated proportion of red blood cell folates (P < 0.03) that is known to be solely represented in those individuals. These results indicate that the MTHFR C677T polymorphism influences DNA methylation status through an interaction with folate status.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.