Proteins mediate numerous biological processes of micronutrients. We have previously defined a plasma nutriproteome as a set of proteins that co-varies with status of a micronutrient indicator with a false discovery rate <10% (Cole et al. J Nutr. 2013). The current study seeks to identify clusters of micronutrients (i.e., defined as >5) whose status indicators co-vary with individual plasma proteins.
We searched the database of the Nepal Nutriproteomics Study which consisted of 982 plasma proteins detected by mass spectrometry in >10% of 500 Nepalese school-aged children.Plasma concentrations of 18 micronutrient indicators (retinol, alpha/gamma-tocopherol, 25(OH)D, PIVKA-II, alpha/beta-carotene, beta-cryptoxanthin, lycopene, lutein, folic acid, homocysteine, pyridoxal-5′-phosphate, cobalamin, transferrin receptor, ferritin, copper, and selenium) were also measured and correlated with protein relative abundance.
A total of 329 proteins were associated with any of 13 micronutrients, of which 24 proteins were associated with = 5 micronutrients. TNFAIP3-interacting protein 1, orosomucoid 1/2, apolipoprotein A-I/A-II/C-IIII, interferon-related developmental regulator, haptoglobin, and anti-trypsin were associated with the largest clusters of micronutrients. Nutrients most frequently correlating with proteins were retinol, vitamin B6, alpha-tocopherol, copper, and beta-cryptoxanthin.Proteins associated with nutrient clusters are involved in diverse homeostatic processes including host defense, inflammation, wound healing and coagulation, nutrient transport (e.g., of retinol, selenium and lipids), and regulation of insulin-like growth factors.
This study reveals shared networks of plasma proteins and micronutrients involved in regulation of homeostasis. The potential public health insights derived from these relationships are discussed. Supported by Grants OPP5241 and GH614 of the Bill and Melinda Gates Foundation.