SynthesisCirculation. Cardiovascular genetics2013
Association between C677T polymorphism of methylene tetrahydrofolate reductase and congenital heart disease: meta-analysis of 7697 cases and 13,125 controls.
Synthesis in Circulation. Cardiovascular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 5 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
21 citing papers in PubMed, 5 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- The Roles of Reduced Folate Carrier-1 (RFC1) A80G (rs1051266) Polymorphism in Congenital Heart Disease: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2021Pooled it
- Mendelian randomisation approaches to the study of prenatal exposures: A systematic review.Paediatric and perinatal epidemiology · 2021Pooled it
- Meta-Prediction of MTHFR Gene Polymorphism and Air Pollution on the Risks of Congenital Heart Defects Worldwide: A Transgenerational Analysis.International journal of environmental research and public health · 2018Pooled it
- Pooled it
- Association between MTHFR polymorphisms and congenital heart disease: a meta-analysis based on 9,329 cases and 15,076 controls.Scientific reports · 2014Pooled it
- The association of the MTHFR c.1625A>C genetic variant with the risk of congenital heart diseases in the Chinese.Genetic testing and molecular biomarkers · 2015Trial
- The impact of nationwide folic acid fortification on genetic variants associated with conotruncal heart defects.Research square · 2026Article
- Association between maternal MTHFR and MTRR gene polymorphisms and the risk of congenital heart disease in newborns.BMC pediatrics · 2026Article
- Translational Genomic Research: The Association between Genetic Profiles and Cognitive Functioning or Cardiac Function Among Breast Cancer Survivors Completing Chemotherapy.Biological research for nursing · 2022Article
- Probing the functional consequence and clinical relevance of CD320 p.E88del, a variant in the transcobalamin receptor gene.American journal of medical genetics. Part A · 2022Article
- Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring.BMC cardiovascular disorders · 2021Article
- Study on Maternal SNPs of MTHFR Gene and HCY Level Related to Congenital Heart Diseases.Pediatric cardiology · 2021Article
- Effectiveness of community-based folate-oriented tertiary interventions on incidence of fetus and birth defects: a protocol for a single-blind cluster randomized controlled trial.BMC pregnancy and childbirth · 2020Article
- Environmental Risk Factors for Congenital Heart Disease.Cold Spring Harbor perspectives in biology · 2020Review
- Association Between Maternal Folic Acid Supplementation and Congenital Heart Defects in Offspring in Birth Cohorts From Denmark and Norway.Journal of the American Heart Association · 2019Article
- Chicken or Egg in the UK Biobank?Circulation research · 2019Article
- Placental epigenetics for evaluation of fetal congenital heart defects: Ventricular Septal Defect (VSD).PloS one · 2019Article
- Recent Advances in Placenta-Heart Interactions.Frontiers in physiology · 2018Review
- Maternal and infant genetic variants, maternal periconceptional use of selective serotonin reuptake inhibitors, and risk of congenital heart defects in offspring: population based study.BMJ (Clinical research ed.) · 2017Article
- Association ofBiomedical reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
42 authors at 7 institutions in 6 countries.
Funding
Abstract
backgroundAssociation between the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and congenital heart disease (CHD) is contentious. METHODS AND
resultsWe compared genotypes between CHD cases and controls and between mothers of CHD cases and controls. We placed our results in context by conducting meta-analyses of previously published studies. Among 5814 cases with primary genotype data and 10 056 controls, there was no evidence of association between MTHFR C677T genotype and CHD risk (odds ratio [OR], 0.96 [95% confidence interval, 0.87-1.07]). A random-effects meta-analysis of all studies (involving 7697 cases and 13 125 controls) suggested the presence of association (OR, 1.25 [95% confidence interval, 1.03-1.51]; P=0.022) but with substantial heterogeneity among contributing studies (I(2)=64.4%) and evidence of publication bias. Meta-analysis of large studies only (defined by a variance of the log OR <0.05), which together contributed 83% of all cases, yielded no evidence of association (OR, 0.97 [95% confidence interval, 0.91-1.03]) without significant heterogeneity (I(2)=0). Moreover, meta-analysis of 1781 mothers of CHD cases (829 of whom were genotyped in this study) and 19 861 controls revealed no evidence of association between maternal C677T genotype and risk of CHD in offspring (OR, 1.13 [95% confidence interval, 0.87-1.47]). There was no significant association between MTHFR genotype and CHD risk in large studies from regions with different levels of dietary folate.
conclusionsThe MTHFR C677T polymorphism, which directly influences plasma folate levels, is not associated with CHD risk. Publication biases appear to substantially contaminate the literature with regard to this genetic association.
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.