title: A Plasma α-Tocopherome Can Be Identified from Proteins Associated with Vitamin E Status in School-Aged Children of Nepal.
abstract: BACKGROUND
  The term vitamin E describes a family of 8 vitamers, 1 of which is α-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 α- and γ-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 (α-tocopherol <12 μmol/L).
  
  
  METHODS
  Study children were born to mothers enrolled in an earlier antenatal micronutrient trial in Sarlahi District, Nepal. Plasma α- and γ-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 α-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 α-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 α-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 γ-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 α-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.
authors.affiliation: Departments of International Health, kwest@jhsph.edu.
authors.forename: Keith P
authors.identifier: http://orcid.org/0000-0001-9458-362X
authors.initials: KP
authors.lastname: West
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine Mass Spectrometry and Proteomics Facility, Baltimore, MD.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Cole
authors.affiliation: Departments of International Health.
authors.forename: Sudeep
authors.initials: S
authors.lastname: Shrestha
authors.affiliation: Departments of International Health.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Schulze
authors.affiliation: Departments of International Health.
authors.forename: Sun Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Biostatistics, and.
authors.forename: Joshua
authors.initials: J
authors.lastname: Betz
authors.affiliation: Departments of International Health.
authors.forename: Bareng As
authors.initials: BA
authors.lastname: Nonyane
authors.affiliation: Departments of International Health.
authors.forename: Lee S-F
authors.initials: LS
authors.lastname: Wu
authors.affiliation: Environmental Health Sciences, Center for Human Nutrition, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and.
authors.forename: James D
authors.initials: JD
authors.lastname: Yager
authors.affiliation: Environmental Health Sciences, Center for Human Nutrition, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and.
authors.forename: John D
authors.initials: JD
authors.lastname: Groopman
authors.affiliation: Departments of International Health.
authors.forename: Parul
authors.initials: P
authors.lastname: Christian
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis*; D002648:Child; D004032:Diet; D019587:Dietary Supplements; D006801:Humans; D044342:Malnutrition / Q000097:blood; D018977:Micronutrients / Q000172:deficiency; D009390:Nepal / Q000453:epidemiology; D009752:Nutritional Status; D040901:Proteomics; D014811:Vitamin E Deficiency / Q000097:blood* / Q000453:epidemiology; D024502:alpha-Tocopherol / Q000097:blood*; D024504:gamma-Tocopherol / Q000097:blood
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D018977:Micronutrients; D024504:gamma-Tocopherol; D024502:alpha-Tocopherol
keywords: Nepal; bioinformatics; micronutrient assessment; plasma proteomics; tocopherome; vitamin E; α-tocopherol; γ-tocopherol