SynthesisPLoS medicine2012
Homocysteine and coronary heart disease: meta-analysis of MTHFR case-control studies, avoiding publication bias.
Synthesis in PLoS medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 8 of them syntheses that pooled it.
What it found
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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.
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, 8 syntheses or guidelines pooled it.
- Associations of the MTHFR rs1801133 polymorphism with coronary artery disease and lipid levels: a systematic review and updated meta-analysis.Lipids in health and disease · 2018Pooled it
- A Meta-Prediction ofInternational journal of environmental research and public health · 2018Pooled it
- Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis.BMC medical genetics · 2015Pooled it
- Correlations of MTHFR 677C>T polymorphism with cardiovascular disease in patients with end-stage renal disease: a meta-analysis.PloS one · 2014Pooled it
- Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.The American journal of clinical nutrition · 2013Pooled it
- Association between C677T polymorphism of methylene tetrahydrofolate reductase and congenital heart disease: meta-analysis of 7697 cases and 13,125 controls.Circulation. Cardiovascular genetics · 2013Pooled it
- Association of methylenetetrahydrofolate reductase gene 677C > T polymorphism and Down syndrome.Molecular biology reports · 2013Pooled it
- Meta-analyses of KIF6 Trp719Arg in coronary heart disease and statin therapeutic effect.PloS one · 2012Pooled it
- Homocysteine levels and treatment effect in the PROspective Study of Pravastatin in the Elderly at Risk.Journal of the American Geriatrics Society · 2014Trial
- Vitamins, Vascular Health and Disease.Nutrients · 2025Review
- Homocysteine, Nutrition, and Gut Microbiota: A Comprehensive Review of Current Evidence and Insights.Nutrients · 2025Review
- Evaluating the Association Between Methylenetetrahydrofolate Reductase (Rs1801131 and Rs1801133) Gene Polymorphisms and Severity of Coronary Lesions in Patients With STEMI and NSTEMI: A Retrospective Cross-Sectional Study.Health science reports · 2025Article
- Analysis of MTHFR C677T genotype and related factors in H-type hypertension in Tibet, China.BMC cardiovascular disorders · 2024Article
- Homocysteine concentration in coronary artery disease and severity of coronary lesions.Journal of cellular and molecular medicine · 2024Article
- Correction of plasma fat-soluble vitamin levels by blood lipids in elderly patients with coronary heart disease.Practical laboratory medicine · 2024Article
- Association between homocysteine and coronary artery disease-trend over time and across the regions: a systematic review and meta-analysis.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Article
- Association Between Plasma Homocysteine Level and Mortality: A Mendelian Randomization Study.Korean circulation journal · 2023Article
- Comprehensive transcriptomics and metabolomics analyses reveal that hyperhomocysteinemia is a high risk factor for coronary artery disease in a chinese obese population aged 40-65: a prospective cross-sectional study.Cardiovascular diabetology · 2023Article
- Ablation of the gut microbiota alleviates high-methionine diet-induced hyperhomocysteinemia and glucose intolerance in mice.NPJ science of food · 2023Article
- SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency.Cellular and molecular life sciences : CMLS · 2022Article
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
32 authors.
Funding
Abstract
backgroundModerately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so "Mendelian randomization" studies using this variant as an instrumental variable could help test causality. METHODS AND
findingsNineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98-1.07; p = 0.28) overall, and 1.01 (0.95-1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09-1.21), significantly discrepant (p = 0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04-1.21) in the 14 larger studies (those with variance of log OR<0.05; total 13,119 cases) and 1.18 (1.09-1.28) in the 72 smaller ones (total 15,498 cases).
conclusionsThe CI for the overall result from large unpublished datasets shows lifelong moderate homocysteine elevation has little or no effect on CHD. The discrepant overall result from previously published studies reflects publication bias or methodological problems.
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