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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.

SUBMITTER: Lee SE

PROVIDER: S-EPMC4840917 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Malnutrition affects body growth, size, and composition of children. Yet, few functional biomarkers are known to be associated with childhood morphology.Objective: This cross-sectional study examined associations of anthropometric indicators of height, musculature, and fat mass with plasma proteins by using proteomics in a population cohort of school-aged Nepalese children.Methods: Height, weight, midupper arm circumference (MUAC), triceps and subscapular skinfolds, upper arm muscle area (AMA), and arm fat area (AFA) were assessed in 500 children 6-8 y of age. Height-for-age z scores (HAZs), weight-for-age z scores (WAZs), and body mass index-for-age z scores (BAZs) were derived from the WHO growth reference. Relative protein abundance was quantified by using tandem mass spectrometry. Protein-anthropometry associations were evaluated by linear mixed-effects models and identified as having a false discovery rate (q) <5%.Results: Among 982 proteins, 1, 10, 14, and 17 proteins were associated with BAZ, HAZ, MUAC, and AMA, respectively (q < 0.05). Insulin-like growth factor (IGF)-I, 2 IGF-binding proteins, and carnosinase-1 were associated with both HAZ and AMA. Proteins involved in nutrient transport, activation of innate immunity, and bone mineralization were associated with HAZ. Several extracellular matrix proteins were positively associated with AMA alone. The proteomes of MUAC and AMA substantially overlapped, whereas no proteins were associated with AFA or triceps and subscapular skinfolds. Myosin light-chain kinase, possibly reflecting leakage from muscle, was inversely associated with BAZ. The proteome of WAZ was the largest (n = 33) and most comprehensive, including proteins involved in neural development and oxidative stress response, among others.Conclusions: Plasma proteomics confirmed known biomarkers of childhood growth and revealed novel proteins associated with lean mass in chronically undernourished children. Identified proteins may serve as candidates for assessing growth and nutritional status of children in similar undernourished settings. The antenatal micronutrient supplementation trial yielding the study cohort of children was registered at clinicaltrials.gov as NCT00115271.

Project description:AbstractAsian Indians have a genetic predisposition to atherothrombotic risk. common carotid intima-media thickness (CCIMT) measured by ultrasound is a quantitative marker for atherosclerotic burden and a derived variable, that is, "CCIMT statistical Z-score (Z-score)" is useful for better quantification. The association between vitamin D deficiency and atherosclerosis is inconclusive. Since, vitamin D deficiency is highly prevalent in India, there is a need to study its relative contribution to subclinical atherosclerotic burden.This prospective cross-sectional study (n = 117) in apparently healthy individuals aged 20 to 60 years sought to identify the determinants of CCIMT Z score with CCIMT measured by "echo-tracking" method. A multivariable linear regression analysis was done with CCIMT Z score as dependent variable and the following as independent variables: age, body mass index, waist-to-height ratio, total cholesterol to HDL ratio (TC-HDL ratio), serum vitamin D3 levels (ng/mL), sex, diabetes mellitus, current cigarette smoking status. A diagnostic prediction model was also developed with a threshold value of 1.96 for CCIMT Z score.The mean (SD) for calendar age (y) was 40 (8). There were 26 (22.22%) individuals in sample with CCIMT Z score ≥1.96 (advanced stage) of whom 14 (23.33%) were <40 y (n = 60). The mean score was 1.28 (90th percentile) in the entire sample. Vitamin D3 deficiency with a mean (SD) blood level (ng/mL) of 14.3 (6.4) was noted and prevalence of deficiency was 81%. The final model wasCCIMT Z-score = 0.80 + (0.841 × current smoking = 1) + (0.156 × TC-HDL ratio) - (0.0263 × vitamin D3 blood level in ng/mL).The decreasing order of association is smoking, TC-HDL ratio, and vitamin D3. With the model, likelihood ratio (95% CIs) was better for positive test 3.5 (1.23-9.94) than that for a negative test 0.83 (0.66-1.02).Internal validation with Bootstrap resampling revealed stability of baseline diagnostic variables.There is substantial subclinical atherosclerotic burden in Indian setting with independent contribution by vitamin D deficiency. The model is valuable in "ruling-in" of the underlying advanced atherosclerosis. The study is limited by convenient sampling and lack of external validation of the model.

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Biological Systems of Vitamin K: A Plasma Nutriproteomics Study of Subclinical Vitamin K Deficiency in 500 Nepalese Children.

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