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.

Plasma proteins associated with circulating carotenoids in Nepalese school-aged children

“…Carotenoids also may have important antioxidant [ 13 ], immunological [ 14 ] or metabolic [ 39 ] functions and thus serve as indicators of general population health [ 40 ]. However, given their infrequent assessment, and strengthening evidence supporting the use of plasma proteomics for assessing population status with respect to other micronutrients [ [23] , [24] , [25] , [26] ], inflammation [ 27 ], cognition [ 28 ] and growth [ 29 ] in this setting, we have revealed in this study protein biomarkers associated with circulating log 2 -normalized concentrations of six common dietary carotenoids which were plausible in their direction and strength of association.…”

“…Of these, 500 samples were randomly chosen for proteomics analysis, maintaining original trial balance. Children from whom samples were selected have been described in detail previously and are typical of children in the region [ [23] , [24] , [25] , [26] , [27] , [28] , [29] , 31 ]. Follow-up data were collected on household socioeconomic characteristics, dietary frequencies and morbidity history for the previous 7 days and anthropometry (weight, height, mid-upper arm circumference), as reported earlier [ 24 ].…”

“…However, as molecules largely detected by chromatographic methods [ 22 ], carotenoids represent a group of micronutrients that are rarely assessed in low-middle income countries, signaling a need to explore novel approaches for their assessment in populations. In exploring plasma proteomics as an approach to ascertain potential biomarkers of micronutrient, functional, and health status in an undernourished population of school-aged children in Nepal, we have revealed associations between clusters of circulating proteins and micronutrient status (vitamins A, E, D and K, copper and selenium) [ [23] , [24] , [25] , [26] ], inflammation [ 27 ], cognition [ 28 ] and anthropometry [ 29 ] in an undernourished population of school-aged children in Nepal. Findings to date suggest that plasma proteomics can identify proteins predictive of nutritional and health status that are candidate biomarkers with the potential to be measured by multi-analyte approaches for protein quantification.…”

Toward Precision Nutrition: Commercial Infant Formulas and Human Milk Compared for Stereospecific Distribution of Fatty Acids Using Metabolomics

“…The nexus of nutrition science and omics systems science technologies, such as nutrigenomics, nutriproteomics, and nutrimetabolomics in particular, offer new ways forward to decipher the components of foodstuff and food supplements (Lee et al, 2016;Pavlidis et al, 2016). The stereospecific analyses of TAGs by chromatographic methods suffer from several limitations, such as acyl migration and laborious and time-consuming performance (Djajasoepena et al, 2015;Ghosh et al, 2016;Karabulut et al, 2007).…”

Routine Supercritical Fluid Chromatography Tandem Mass Spectrometry Method for Determination of Vitamin K1 Extracted from Serum with a 96-Well Solid-Phase Extraction Method

“…Serum concentration of vitamin K1 is an indicator of vitamin K status, which directly reflects storage and transport of vitamin K (5). Several methods for determining vitamin K1 have been published, mostly with extensive sample preparation using liquid chromatography (LC) 3 coupled with fluorescence detection or mass spectrometry (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”