ArticleThe American journal of clinical nutrition2018
The 677C→T variant of MTHFR is the major genetic modifier of biomarkers of folate status in a young, healthy Irish population.
Article in The American journal of clinical nutrition, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Genetic Variants Shaping Inter-individual Differences in Response to Dietary Intakes-A Narrative Review of the Case of Vitamins.Frontiers in nutrition · 2020Pooled it
- Folic Acid and Endothelial Dysfunction in COVID-19.Life (Basel, Switzerland) · 2026Review
- Metabolomics and Human Health: Progress, Insights, Challenges and the Concept of a Healthy Metabolome.Biomolecules · 2026Review
- Erythrocyte Folate and Homocysteine in Hypertensive Disorders of Pregnancy: Associations with Pregnancy Outcomes.International journal of women's health · 2026Article
- Unraveling folate deficiency: prevalence, biochemical associations, genetic determinants, and strategies for adolescent health in North India.European journal of clinical nutrition · 2025Article
- The Interrelationship between Preconception Folate Nutritional Intake and Child Genetic Liability in the Risk of Childhood Acute Lymphoblastic Leukemia.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Article
- Folate intake,The British journal of nutrition · 2025Article
- Factors Underlying Failure of Methotrexate Treatment in Rheumatoid Arthritis: Implications in Personalized Care.Archives of internal medicine research · 2025Article
- Understanding the Genetic Architecture of Vitamin Status Biomarkers in the Genome-Wide Association Study Era: Biological Insights and Clinical Significance.Advances in nutrition (Bethesda, Md.) · 2024Review
- Invited Perspective: Protect and Serve-The Potential Role of Folate in Lead Risk Reduction.Environmental health perspectives · 2024Article
- A Proactive Intervention Study in Metabolic Syndrome High-Risk Populations Using Phenome-Based Actionable P4 Medicine Strategy.Phenomics (Cham, Switzerland) · 2024Article
- Scientific opinion on the tolerable upper intake level for folate.EFSA journal. European Food Safety Authority · 2023Article
- Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?The American journal of clinical nutrition · 2023Article
- Can Pharmacogenetic Variants inInternational journal of molecular sciences · 2023Article
- Article
- Genetic polymorphism inSkin health and disease · 2022Article
- Associations between Genetic Variants and Blood Biomarkers of One-Carbon Metabolism in Postmenopausal Women from the Women's Health Initiative Observational Study.The Journal of nutrition · 2022Observational
- Exome-Wide Association Study Identifies East Asian-Specific Missense VariantFrontiers in genetics · 2021Article
- Methylenetetrahydrofolate Reductase GeneFrontiers in cardiovascular medicine · 2021Article
- Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework.Nutrients · 2020Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Background: Genetic polymorphisms can explain some of the population- and individual-based variations in nutritional status biomarkers. Objective: We sought to screen the entire human genome for common genetic polymorphisms that influence folate-status biomarkers in healthy individuals. Design: We carried out candidate gene analyses and genome-wide association scans in 2232 young, healthy Irish subjects to evaluate which common genetic polymorphisms influence red blood cell folate, serum folate, and plasma total homocysteine. Results: The 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T (rs1801133) variant was the major genetic modifier of all 3 folate-related biomarkers in this Irish population and reached genome-wide significance for red blood cell folate (P = 1.37 × 10-17), serum folate (P = 2.82 × 10-11), and plasma total homocysteine (P = 1.26 × 10-19) concentrations. A second polymorphism in the MTHFR gene (rs3753584, P = 1.09 × 10-11) was the only additional MTHFR variant to exhibit any significant independent effect on red blood cell folate. Other MTHFR variants, including the 1298A→C variant (rs1801131), appeared to reach genome-wide significance, but these variants shared linkage disequilibrium with MTHFR 677C→T and were not significant when analyzed in MTHFR 677CC homozygotes. No additional non-MTHFR modifiers of red blood cell or plasma folate were detected. Two additional genome-wide significant modifiers of plasma homocysteine were found in the region of the dipeptidase 1 (DPEP1) gene on chromosome 16 and the Twist neighbor B (TWISTNB) gene on chromosome 7. Conclusions: The MTHFR 677C→T variant is the predominant genetic modifier of folate status biomarkers in this healthy Irish population. It is not necessary to determine MTHFR 677C→T genotype to evaluate folate status because its effect is reflected in concentrations of standard folate biomarkers. The MTHFR 1298A→C variant had no independent effect on folate status biomarkers. To our knowledge, this is the first genome-wide association study report on red blood cell folate and the first report of an association between homocysteine and TWISTNB.
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