title: Biological Systems of Vitamin K: A Plasma Nutriproteomics Study of Subclinical Vitamin K Deficiency in 500 Nepalese Children.
abstract: Vitamin K (VK) is a fat-soluble vitamin whose deficiency disrupts coagulation and may disturb bone and cardiovascular health. However, the scale and systems affected by VK deficiency in pediatric populations remains unclear. We conducted a study of the plasma proteome of 500 Nepalese children 6-8 years of age (male/female ratio = 0.99) to identify proteins associated with VK status. We measured the concentrations of plasma lipids and protein induced by VK absence-II (PIVKA-II) and correlated relative abundance of proteins quantified by mass spectrometry with PIVKA-II. VK deficiency (PIVKA-II>2 μg/L) was associated with a higher abundance of low-density lipoproteins, total cholesterol, and triglyceride concentrations (p<0.01). Among 978 proteins observed in >10% of the children, five proteins were associated with PIVKA-II and seven proteins were differentially abundant between VK deficient versus sufficient children, including coagulation factor-II, hemoglobin, and vascular endothelial cadherin, passing a false discovery rate (FDR) threshold of 10% (q<0.10). Among 27 proteins associated with PIVKA-II or VK deficiency at a less stringent FDR (q<0.20), a network comprised of hemoglobin subunits and erythrocyte anti-oxidative enzymes were highly and positively correlated each other (all r>0.7). Untargeted proteomics offers a novel systems approach to elucidating biological processes of coagulation, vascularization, and erythrocyte oxidative stress related to VK status. The results may help elucidate subclinical metabolic disturbances related to VK deficiency in populations.
authors.affiliation: 1 Center for Human Nutrition, Departments of International Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Sun Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: 1 Center for Human Nutrition, Departments of International Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Schulze
authors.affiliation: 2 Mass Spectrometry and Proteomics Core Facility, Department of Biological Chemistry, Johns Hopkins School of Medicine , Baltimore, Maryland.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Cole
authors.affiliation: 1 Center for Human Nutrition, Departments of International Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Lee S F
authors.initials: LS
authors.lastname: Wu
authors.affiliation: 3 Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: James D
authors.initials: JD
authors.lastname: Yager
authors.affiliation: 3 Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: John
authors.initials: J
authors.lastname: Groopman
authors.affiliation: 1 Center for Human Nutrition, Departments of International Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Parul
authors.initials: P
authors.lastname: Christian
authors.affiliation: 1 Center for Human Nutrition, Departments of International Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
authors.forename: Keith P
authors.initials: KP
authors.lastname: West
mesh_terms: D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D009390:Nepal / Q000453:epidemiology; D014813:Vitamin K Deficiency / Q000453:epidemiology*