title: Plasma Selenium Protein P Isoform 1 (SEPP1): A Predictor of Selenium Status in Nepalese Children Detected by Plasma Proteomics.
abstract: Selenium deficiency or excess may have public health consequences, yet selenium status is infrequently characterized in populations, perhaps due to challenges in methodology. We are seeking to identify plasma proteins, using proteomics discovery and validation approaches, to serve as proxies for micronutrient status, including selenium, which may in the future be more readily assessed by robust, affordable field methods. In a sample of rural Nepalese children 6 - 8 years old (n = 500), the prevalence of selenium deficiency was 13.6 and 60.9 % at plasma selenium concentrations < 0.60 and < 0.89 µmol/L, respectively, assessed by atomic absorption spectroscopy. Relative abundance of selenoprotein P isoform 1 (SEPP1), glutathione reductase-3, and apolipoprotein A2 from discovery-based experiments was correlated with plasma selenium with a false discovery rate < 10 % (i. e., q < 0.10), all with p < 0.001. In linear mixed effects regression models to predict plasma selenium, only SEPP1 was significant (R2= 0.63), estimating 8.2 % (95 % CI: 3.9 - 12.6) and 65.5(61.4 - 69.7)% of the in-sample population as deficient at each respective cut-off. Targeted quantification of SEPP1 in a preliminary series of specimens (n = 19) as a validation of the discovery approach revealed a high correlation with plasma selenium (r = 0.757, p = 0.0002). Plasma proteomics can identify valid plasma protein indicators of micronutrient status, as shown with selenium, comprising a step toward making population assessment of selenium status in vulnerable groups more accessible.
authors.affiliation: 1 Center for Human Nutrition, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Schulze
authors.affiliation: 2 Mass Spectrometry and Proteomics Core Facility, Department of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Cole
authors.affiliation: 2 Mass Spectrometry and Proteomics Core Facility, Department of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Raghothama
authors.initials: R
authors.lastname: Chaerkady
authors.affiliation: 1 Center for Human Nutrition, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Lee S F
authors.initials: LSF
authors.lastname: Wu
authors.affiliation: 3 Program in Global Disease Epidemiology and Control, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Bareng A S
authors.initials: BAS
authors.lastname: Nonyane
authors.affiliation: 1 Center for Human Nutrition, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Sun Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: 4 Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Yager
authors.affiliation: 4 Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Groopman
authors.affiliation: 1 Center for Human Nutrition, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Parul
authors.initials: P
authors.lastname: Christian
authors.affiliation: 1 Center for Human Nutrition, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Keith P
authors.initials: KP
authors.lastname: West
keywords: Nepal; apolipoprotein; glutathione reductase (GPX); micronutrient assessment; proteomics; selenium; selenoprotein P isoform 1 (SEPP1)