Omic markers identification for predicting risks of negative effects in children with elevated copper and nickel contents in blood

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Proteomic profiling is a promising procedure for examining and substantiating molecular mechanisms of body reactions occurrence and development as a response to adverse impacts; it allows detecting and examining these reactions at early stages in their development prior to cellular damage and damage to organs. Studies aimed at increasing efficiency of adverse effects prediction are especially vital for solving tasks related to early detection and prevention of consequences associated with exposure to chemical environmental factors, first of all, ambient air. Our research goal was to identify omic-markers for predicting risks of negative effects in children with elevated copper and nickel contents in blood. We performed proteomic blood plasma examination in children and modeled cause-and-effect relations. Children with copper and nickel contents in their blood being 3.5 times higher than physiological standard had approximately 20 protein stains that were authentically different from those detected in children from the reference group. We detected correlations between an increase in relative volume of three protein stains including apolipoprotein A-I, anchor protein of A-kinase 9, vitronectin, and a decrease in relative volume of one protein strain including transthyretin and elevated copper and nickel contents in blood (R2=0.30–0.44; р=0.0001–0.008). All the above-mentioned proteins have predictive significance when it comes down to negative effects related to neuroregulation disorders and endothelial dysfunction. It was proven that there was a risk of predicted negative effects such as greater frequency of nervous and cardiovascular system diseases in case copper and nickel contents in blood were elevated (R2=0.35–0.96; р=0.0001–0.013). The established list of potential target molecules (apolipoprotein A-I, vitronectin, anchor protein of A-kinase 9, and transthyretin) and genes that coded their expression (APOA1, VTN,AKAP9,TTR) was substantiated as omic-markers indicating a possibility that negative effects might occur in the cardiovascular and nervous system.