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A Plasma Retinome in School Aged Children of Nepal
Author(s) -
West Keith P.,
Cole Robert N.,
Schulze Kerry,
Ruczinski Ingo,
Christian Parul,
Shrestha Sudeep,
Wu Lee,
Yager James,
Groopman John D.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.392.6
Subject(s) - transthyretin , retinol , vitamin , blood proteins , population , human plasma , medicine , chemistry , endocrinology , biology , chromatography , environmental health
Vitamin A (VA) deficiency remains a major public health concern. Yet its assessment remains difficult, leaving evidence gaps for program targeting and evaluation. We are exploring the existence and validity of a plasma retinome as a novel basis for assessing future population VA status. Plasma samples from Nepalese children 6–8 yrs (n=280 to date) were obtained, processed, transported and stored by standard methods, analyzed by HPLC for retinol (mean + SD = 1.03±0.27 μmol/L) and mined by tandem MS iTRAQ and bioinformatics analyses to identify and quantify relative abundance of plasma proteins. Of 293 unique proteins identified in all subjects with 95% confidence, 88 are correlated with retinol [p<0.05, p (false discovery) = q <0.08; 62 at p<0.01 and q<0.01]. Strong correlations with retinol‐binding protein 4 (p=1.30E‐45; q=1.99E‐43, r2 =0.52, r=0.72), transthyretin (p=1.64E‐22; q=1.25E‐20, r2 =0.29, r=0.54) and apoliproteins A and C (all p< 2.15E‐07 ; q<3.00E‐06, r2>0.09, r>0.30 ), and a plethora of negatively correlated acute phase biomarkers, reveal a valid plasma retinome. Based on functional annotation clustering (DAVID Bioinformatics Resources, v6.7) proteins in the plasma retinome are associated with signaling [enrichment score (ES) 38.05 ), host defenses, complement and coagulation cascade (ES 8.13 ), lipid transport (ES 4.9), enzyme inhibition (ES 8.9) and proteolysis (ES 5.65 ). A large number of diverse, covarying proteins reveals the complexity of VA biology and a potentially predictive plasma retinome. Funded by the Bill and Melinda Gates Foundation (Grant GH 5241).