Epigenome-wide association study reveals a molecular signature of response to phylloquinone (vitaminK1) supplementation

Authors: WESTERMAN, KENNETH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; KELLY, JENNIFER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DEMEO, DAWN - Brigham & Women'S Hospital

Submitted to: Epigenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/11/2020
Publication Date: 3/5/2020
Citation: Westerman, K., Kelly, J.M., Ordovas, J.M., Booth, S.L., DeMeo, D.F. 2020. Epigenome-wide association study reveals a molecular signature of response to phylloquinone (vitaminK1) supplementation. Epigenetics. 15(8):859-870. https://doi.org/10.1080/15592294.2020.1734714.
DOI: https://doi.org/10.1080/15592294.2020.1734714

Interpretive Summary: Vitamin K plays a role in various chronic disease outcomes. Still, population-level diet and supplement recommendations are difficult to determine due to high variability in measures of status and response to intake compared to other nutrients. In this preliminary investigation, scientists at the HNRCA in Boston carried out a methylation study comparing responders and non-responders to phylloquinone (vitamin K1) supplementation to better understand the molecular bases of the observed variability in response. DNA methylation is a biological process that adds methyl groups to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. This study identified differential DNA methylation in multiple regions with previously unknown relationships to vitamin K1 absorption and metabolism. Furthermore, an analysis for baseline plasma vitamin K1 concentrations revealed a strong correlation between the methylation signatures of baseline vitamin K1 status and response to supplementation. This work can guide future research on vitamin K and contribute to developing more personalized dietary recommendations for vitamin K.

Technical Abstract: Evidence suggests there are roles for vitamin K in various chronic disease outcomes, but population-level diet and supplement recommendations are difficult to determine due to high levels of variability in measures of status and response to intake compared to other nutrients. In this preliminary investigation, a blood-based epigenome-wide association study (EWAS) comparing responders and non-responders to phylloquinone (vitamin K1) supplementation (NCT00183001) was undertaken in order to better understand the molecular underpinnings of this observed variability. Responders (n = 24) and non-responders (n = 24) were identified in a prior 3-year phylloquinone supplementation trial based on their changes in plasma phylloquinone concentrations. Differential DNA methylation was identified in multiple regions with previously unknown relationships to phylloquinone absorption and metabolism, such as at the TMEM263 locus. A hypothesis-driven analysis of lipid-related genes highlighted a site in the NPC1L1 gene, supplementing existing evidence for its role in phylloquinone absorption. Furthermore, an EWAS for baseline plasma phylloquinone concentrations revealed a strong correlation between the epigenomic signatures of phylloquinone baseline status and response to supplementation. This work can guide future epigenomic research on vitamin K and contributes to the development of more personalized dietary recommendations for vitamin K.