TY - JOUR
T1 - The plasma proteome identifies expected and novel proteins correlated with micronutrient status in undernourished nepalese children1-3
AU - Cole, Robert N.
AU - Ruczinski, Ingo
AU - Schulze, Kerry
AU - Christian, Parul
AU - Herbrich, Shelley
AU - Wu, Lee
AU - DeVine, Lauren R.
AU - O'Meally, Robert N.
AU - Shrestha, Sudeep
AU - Boronina, Tatiana N.
AU - Yager, James D.
AU - Groopman, John
AU - West, Keith P.
PY - 2013
Y1 - 2013
N2 - Micronutrient deficiencies are common in undernourished societies yet remain inadequately assessed due to the complexity and costs of existing assays. A plasma proteomics-based approach holds promise in quantifying multiple nutrient:protein associations that reflect biological function and nutritional status. To validate this concept, in plasma samples of a cohort of 500 6- to 8-y-old Nepalese children, we estimated cross-sectional correlations between vitamins A (retinol), D (25-hydroxyvitamin D), and E (a-tocopherol), copper, and selenium, measured by conventional assays, and relative abundance of their major plasmabound proteins, measured by quantitative proteomics using 8-plex iTRAQ mass tags. The prevalence of low-to-deficient status was 8.8% (<0.70 μmol/L) for retinol, 19.2% (<50 nmol/L) for 25-hydroxyvitamin D, 17.6% (<9.3 μmol/L) for a-tocopherol, 0% (<10 mmol/L) for copper, and 13.6% (<0.6 μmol/L) for selenium.We identified 4705 proteins, 982 in >50 children. Employing a linear mixed effectsmodel, we observed the following correlations: retinol:retinol-binding protein 4 (r = 0.88), 25-hydroxyvitamin D:vitamin D-binding protein (r = 0.58), α-tocopherol:apolipoprotein C-III (r = 0.64), copper:ceruloplasmin (r = 0.65), and selenium: selenoprotein P isoform 1 (r = 0.79) (all P < 0.0001), passing a false discovery rate threshold of 1% (based on P value-derived q values). Individual proteins explained 34-77% (R2) of variation in their respective nutrient concentration. Adding second proteins to models raised R2 to 48-79%, demonstrating a potential to explain additional variation in nutrient concentration by this strategy. Plasma proteomics can identify and quantify protein biomarkers of micronutrient status in undernourished children. The maternalmicronutrient supplementation trial, fromwhich data were derived as a follow-up activity,was registered at clinicaltrials. gov as NCT00115271. 2013.
AB - Micronutrient deficiencies are common in undernourished societies yet remain inadequately assessed due to the complexity and costs of existing assays. A plasma proteomics-based approach holds promise in quantifying multiple nutrient:protein associations that reflect biological function and nutritional status. To validate this concept, in plasma samples of a cohort of 500 6- to 8-y-old Nepalese children, we estimated cross-sectional correlations between vitamins A (retinol), D (25-hydroxyvitamin D), and E (a-tocopherol), copper, and selenium, measured by conventional assays, and relative abundance of their major plasmabound proteins, measured by quantitative proteomics using 8-plex iTRAQ mass tags. The prevalence of low-to-deficient status was 8.8% (<0.70 μmol/L) for retinol, 19.2% (<50 nmol/L) for 25-hydroxyvitamin D, 17.6% (<9.3 μmol/L) for a-tocopherol, 0% (<10 mmol/L) for copper, and 13.6% (<0.6 μmol/L) for selenium.We identified 4705 proteins, 982 in >50 children. Employing a linear mixed effectsmodel, we observed the following correlations: retinol:retinol-binding protein 4 (r = 0.88), 25-hydroxyvitamin D:vitamin D-binding protein (r = 0.58), α-tocopherol:apolipoprotein C-III (r = 0.64), copper:ceruloplasmin (r = 0.65), and selenium: selenoprotein P isoform 1 (r = 0.79) (all P < 0.0001), passing a false discovery rate threshold of 1% (based on P value-derived q values). Individual proteins explained 34-77% (R2) of variation in their respective nutrient concentration. Adding second proteins to models raised R2 to 48-79%, demonstrating a potential to explain additional variation in nutrient concentration by this strategy. Plasma proteomics can identify and quantify protein biomarkers of micronutrient status in undernourished children. The maternalmicronutrient supplementation trial, fromwhich data were derived as a follow-up activity,was registered at clinicaltrials. gov as NCT00115271. 2013.
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U2 - 10.3945/jn.113.175018
DO - 10.3945/jn.113.175018
M3 - Article
C2 - 23966331
AN - SCOPUS:84885734352
SN - 0022-3166
VL - 143
SP - 1540
EP - 1548
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 10
ER -