ArticleClinical nutrition (Edinburgh, Scotland)2020
Circulating phylloquinone, inactive Matrix Gla protein and coronary heart disease risk: A two-sample Mendelian Randomization study.
Article in Clinical nutrition (Edinburgh, Scotland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Vitamin K: Metabolism, Genetic Influences, and Chronic Disease Outcomes.Food science & nutrition · 2025Review
- Inactive Matrix Gla Protein and Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis.Journal of the American Heart Association · 2025Article
- Vitamin K Properties in Stroke and Alzheimer's Disease: A Janus Bifrons in Protection and Prevention.Molecules (Basel, Switzerland) · 2025Review
- The associations between functional vitamin K status and all-cause mortality, cardiovascular disease and end-stage kidney disease in persons with type 1 diabetes.Diabetes, obesity & metabolism · 2025Article
- New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy.Arquivos brasileiros de cardiologia · 2023Article
- The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence.Frontiers in cardiovascular medicine · 2023Article
- Vitamin K-Dependent Protein Activation: Normal Gamma-Glutamyl Carboxylation and Disruption in Disease.International journal of molecular sciences · 2022Review
- Vitamin KOpen heart · 2021Review
- Vitamin K & D Deficiencies Are Independently Associated With COVID-19 Disease Severity.Open forum infectious diseases · 2021Article
- Circulating Alpha-Tocopherol Levels, Bone Mineral Density, and Fracture: Mendelian Randomization Study.Nutrients · 2021Article
- The Dual Role of Vitamin K2 in "Bone-Vascular Crosstalk": Opposite Effects on Bone Loss and Vascular Calcification.Nutrients · 2021Review
- Vitamin and Mineral Status in a Vegan Diet.Deutsches Arzteblatt international · 2020Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
aimsMultiple observational studies and small-scale intervention studies suggest that high vitamin K intake is associated with improved markers for cardiovascular health. Circulating phylloquinone solely represents phylloquinone (vitamin K1) intake, while dephosphorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) represents both phylloquinone and menaquinone (vitamin K2) intake. This study aims to investigate the causal relationship between genetically predicted vitamin K concentrations and the risk of CHD via a two-sample Mendelian Randomization approach.
designWe used data from three studies: the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study, CARDIOGRAMplusC4D and the UK Biobank, resulting in 103,097 CHD cases. Genetically predicted vitamin K concentrations were measured using SNPs related to circulating phylloquinone and dp-ucMGP. We calculated a genetic risk score (GRS) including four SNPs (rs2108622, rs2192574, rs4645543 and rs6862071) related to circulating phylloquinone levels from a genome wide association study. Rs4236 was used as an instrumental variable for dp-ucMGP. Inverse-variance weighted (IVW) analysis was used to obtain Risk Ratios (RRs) for the causal relationship between phylloquinone and dp-ucMGP concentrations and CHD risk.
resultsUsing the genetic score for circulating phylloquinone, we found that circulating phylloquinone was not causally related to CHD risk (RR 1.00 (95%-CI: 0.98; 1.04)). Lower genetically predicted dp-ucMGP concentration was associated with a lower CHD risk with a RR of 0.96 (95%-CI: 0.93; 0.99) for every 10 μg/L decrease in dp-ucMGP.
conclusionsThis study did not confirm a causal relationship between circulating phylloquinone and lower CHD risk. However, lower dp-ucMGP levels may be causally related with a decreased CHD risk. This inconsistent result may reflect the influence of menaquinones in the association with CHD.
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