ArticleAmerican journal of human genetics2002
A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group.
Article in American journal of human genetics, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 4 syntheses or guidelines pooled it, 234 citations in OpenAlex.
- MTHFD1 polymorphism as maternal risk for neural tube defects: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2015Pooled it
- Lack of association between MTHFD1 G401A polymorphism and ovarian cancer susceptibility.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Association between MTHFD1 G1958A polymorphism and neural tube defects susceptibility: a meta-analysis.PloS one · 2014Pooled it
- Association of methylenetetrahydrofolate dehydrogenase 1 polymorphisms with cancer: a meta-analysis.PloS one · 2013Pooled it
- Low folate status and related polymorphisms are associated with lower sperm quality in healthy males: The Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters (Led-Fertyl) cross-sectional study.The American journal of clinical nutrition · 2026Article
- Spina bifida as a multifactorial birth defect: Risk factors and genetic underpinnings.Pediatric discovery · 2025Review
- Cellular and organismal function of choline metabolism.Nature metabolism · 2025Review
- Article
- Relationship between MTHFR gene polymorphism and risk of thrombosis in postoperative patients with colorectal cancer.Experimental and therapeutic medicine · 2023Article
- Spina Bifida: A Review of the Genetics, Pathophysiology and Emerging Cellular Therapies.Journal of developmental biology · 2022Review
- Methyl Metabolism and the Clock: An Ancient Story With New Perspectives.Journal of biological rhythms · 2022Article
- Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.BMC pregnancy and childbirth · 2022Article
- Association of Maternal Dietary Habits andFrontiers in pediatrics · 2021Article
- Gene-based analyses of the maternal genome implicate maternal effect genes as risk factors for conotruncal heart defects.PloS one · 2020Article
- Article
- Methylenetetrahydrofolate Dehydrogenase 1 (MTHFD1) is Underexpressed in Clear Cell Renal Cell Carcinoma Tissue and Transfection and Overexpression in Caki-1 Cells Inhibits Cell Proliferation and Increases Apoptosis.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Nuclear Folate Metabolism.Annual review of nutrition · 2018Review
- Targeting nuclear thymidylate biosynthesis.Molecular aspects of medicine · 2017Review
- One-carbon genetic variants and the role of MTHFD1 1958G>A in liver and colon cancer risk according to global DNA methylation.PloS one · 2017Article
- Evaluation of proton-coupled folate transporter (SLC46A1) polymorphisms as risk factors for neural tube defects and oral clefts.American journal of medical genetics. Part A · 2016Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Women who take folic acid periconceptionally reduce their risk of having a child with a neural tube defect (NTD) by >50%. A variant form of methylenetetrahydrofolate reductase (MTHFR) (677C-->T) is a known risk factor for NTDs, but the prevalence of the risk genotype explains only a small portion of the protective effect of folic acid. This has prompted the search for additional NTD-associated variants in folate-metabolism enzymes. We have analyzed five potential single-nucleotide polymorphisms (SNPs) in the cytoplasmic, nicotinamide adenine dinucleotide phosphate-dependent, trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase (MTHFD1) for an association with NTDs in the Irish population. One SNP, R653Q, in this gene appears to be associated with NTD risk. We observed an excess of the MTHFD1 "Q" allele in the mothers of children with NTD, compared with control individuals. This excess was driven by the overrepresentation of QQ homozygotes in the mothers of children with NTD compared with control individuals (odds ratio 1.52 [95% confidence interval 1.16-1.99], P=.003). We conclude that genetic variation in the MTHFD1 gene is associated with an increase in the genetically determined risk that a woman will bear a child with NTD and that the gene may be associated with decreased embryo survival.
Indexed as
Identifiers
What OpenQuestion holds
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.