The Plasma Proteome Is Associated with Anthropometric Status of Undernourished Nepalese School-Aged Children

Sun Eun Lee, Christine P. Stewart, Kerry J. Schulze, Robert N. Cole, Lee S.F. Wu, James D. Yager, John D. Groopman, Subarna K. Khatry, Ramesh Kant Adhikari, Parul Christian, Keith P. West

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)304-313
Number of pages10
JournalThe Journal of nutrition
Volume147
Issue number3
DOIs
StatePublished - Mar 1 2017

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Proteome
Arm
Muscles
Proteins
Fats
Growth
Proteomics
Biomarkers
Myosin-Light-Chain Kinase
Insulin-Like Growth Factor Binding Protein 1
Weights and Measures
Physiologic Calcification
Anthropometry
Micronutrients
Extracellular Matrix Proteins
Body Size
Tandem Mass Spectrometry
Body Composition
Nutritional Status
Insulin-Like Growth Factor I

Keywords

  • anthropometry
  • children
  • insulin-like growth factor I
  • insulin-like growth factor–binding proteins
  • mass spectrometry
  • Nepal
  • plasma proteome

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

@article{c89e008ca999412da03d68103322c0fc,
title = "The Plasma Proteome Is Associated with Anthropometric Status of Undernourished Nepalese School-Aged Children",
abstract = "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.",
keywords = "anthropometry, children, insulin-like growth factor I, insulin-like growth factor–binding proteins, mass spectrometry, Nepal, plasma proteome",
author = "Lee, {Sun Eun} and Stewart, {Christine P.} and Schulze, {Kerry J.} and Cole, {Robert N.} and Wu, {Lee S.F.} and Yager, {James D.} and Groopman, {John D.} and Khatry, {Subarna K.} and Adhikari, {Ramesh Kant} and Parul Christian and West, {Keith P.}",
year = "2017",
month = "3",
day = "1",
doi = "10.3945/jn.116.243014",
language = "English (US)",
volume = "147",
pages = "304--313",
journal = "Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "3",

}

TY - JOUR

T1 - The Plasma Proteome Is Associated with Anthropometric Status of Undernourished Nepalese School-Aged Children

AU - Lee, Sun Eun

AU - Stewart, Christine P.

AU - Schulze, Kerry J.

AU - Cole, Robert N.

AU - Wu, Lee S.F.

AU - Yager, James D.

AU - Groopman, John D.

AU - Khatry, Subarna K.

AU - Adhikari, Ramesh Kant

AU - Christian, Parul

AU - West, Keith P.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

KW - anthropometry

KW - children

KW - insulin-like growth factor I

KW - insulin-like growth factor–binding proteins

KW - mass spectrometry

KW - Nepal

KW - plasma proteome

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U2 - 10.3945/jn.116.243014

DO - 10.3945/jn.116.243014

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JO - Journal of Nutrition

JF - Journal of Nutrition

SN - 0022-3166

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