A Plasma alpha-Tocopherome Can Be Identified from Proteins Associated with Vitamin E Status in School-Aged Children of Nepal

卷:145

West, Keith P., Jr. ; Cole, Robert N. ; Shrestha, Sudeep ; Schulze, Kerry J. ; Lee, Sun Eun ; Betz, Joshua ; Nonyane, Bareng A. S. ; Wu, Lee S-F ; Yager, James D. ; Groopman, John D. ; Christian, Parul

关键词: vitamin E;    alpha-tocopherol;    gamma-tocopherol;    tocopherome;    plasma proteomics;    bioinformatics;    micronutrient assessment;    Nepal;   

DOI  :  10.3945/jn.115.210682

学科分类：食品科学和技术

【 摘 要 】

Background: The term vitamin E describes a family of 8 vitamers, 1 of which is a-tocopherol, that is essential for human health. Vitamin E status remains largely unknown in low-income countries because of the complexity and cost of measurement. Quantitative proteomics may offer an approach for identifying plasma proteins for assessing vitamin E status in these populations. Objective: To improve options for vitamin E status assessment, we sought to detect and quantify a set of plasma proteins associated with alpha -and gamma-tocopherol concentrations in a cohort of 500 rural Nepalese children aged 6-8 y and, based on nutrient-protein associations, to predict the prevalence of vitamin E deficiency (alpha-tocopherol < 12 mu mol/L). Methods: Study children were born to mothers enrolled in an earlier antenatal micronutrient trial in Sarlahi District, Nepal. Plasma alpha -and gamma-tocopherol concentrations were measured by high-performance liquid chromatography. Plasma aliquots were depleted of 6 high-abundance proteins, digested with trypsin, labeled with isobaric mass tags, and assessed for relative protein abundance by tandem mass spectrometry. Linear mixed-effects models were used to evaluate the association between a-tocopherol status and relative protein abundance and to predict deficiency. Results: We quantified 982 plasma proteins in >10% of all child samples, of which 119 correlated with a-tocopherol (false discovery rate, q < 0.10). Proteins were primarily involved in lipid transport, coagulation, repair, innate host defenses, neural function, and homeostasis. Six proteins [apolipoprotein (apo) C-III; apoB; pyruvate kinase, muscle; forkhead box 04; unc5 homolog C; and regulator of G-protein signaling 8] explained 71% of the variability in plasma a-tocopherol, predicting an in-sample population prevalence of vitamin E deficiency of 51.4% (95% CI: 46.4%, 56.3%) compared with a measured prevalence of 54.8%. Plasma g-tocopherol was associated with 12 proteins (q < 0.10), 2 of which (apoC-III and Misato 1) explained 20% of its variability. Conclusions: In this undernourished population of children in South Asia, quantitative proteomics identified a large plasma alpha-tocopherome from which 6 proteins predicted the prevalence of vitamin E deficiency. The findings illustrate that protein biomarkers, once absolutely quantified, can potentially predict micronutrient deficiencies in populations. The maternal micronutrient supplementation trial from which data were derived as a follow-up activity was registered with clinicaltrials. gov as NCT00115271.