SAT-017 Emerging Biomarkers in Vitamin D Metabolism

The pleiotropic effects of vitamin D, specifically its extra-skeletal effects, remains controversial, despite an abundance of existing literature. Through biomarker discovery using 3D LC-nESI-FTMS quantitative proteomics, we revealed the different signature proteins activated by vitamin D that is influenced by sex and vitamin D status. The present studies included vitamin D deficient Saudi adults recruited from several centers and is divided into 3 phases: (1) biomarker discovery phase through profiling of pooled serum proteomes (males=31; females=28); (2) vitamin D biomarker discovery using the same depletion-free quantitative proteomics among vitamin D deficient subjects (males=26; females=24) that achieved vitamin D correction after 12-month vitamin D correction and (3) biomarker validation phase of 35 most significantly modulated signature proteins using enzyme-linked immunosorbent assays from 259 vitamin D deficient participants stratified according to response to 6-month vitamin D supplementation [Responders: (25(OH)D >50nmol/l, N=162 (70 males; 92 females); Non-responders: 25(OH)D <50nmol/l, N=97 (27 males; 70 females)]. The first phase identified 2472 reproducible proteins, among which 248 exhibited significant modulation between men and women that mapped pathways associated with several key metabolic pathways including vitamin D function. The second phase identified 282 proteins that were differentially expressed between men and women after vitamin D intervention. The most significant biomarkers identified included those from the coagulation pathway, lipids, apolipoproteins, inflammatory markers, insulin growth factors and other proteins. The last phase confirmed the associations of the identified biomarkers only among those whose vitamin D status responded to vitamin D status correction. Our series of studies confirm the importance of vitamin D in human metabolism at the proteomic level and the significant expression of major clinical biomarkers and their respective metabolic pathways depending on vitamin D supplementation response.