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Influence of genetic polymorphisms in SEPP1 gene on SePP and GPx3 concentrations after Brazil nut supplementation

Grant number: 15/10146-8
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): August 01, 2015
Effective date (End): November 30, 2015
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal Investigator:Silvia Maria Franciscato Cozzolino
Grantee:Janaina Lombello Santos Donadio
Supervisor: John Edward Hesketh
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Newcastle University, England  
Associated to the scholarship:11/17720-0 - Influence of diferents genotypes in the pattern of selenoproteins expression in response to selenium supplementation, BP.DR


BACKGROUND: Selenium (Se) is essential for human health, being inserted in 25 selenoproteins as the amino acid selenocysteine. Its most famous function is its antioxidant role, but Se is also related to improve immune function, reducing risk of cardiovascular disease, cancer and diabetes mellitus type 2. Brazil nuts are known as the richest food source of Se, considered one of the most nutritious food, as a result of its high content of protein, polyunsaturated fatty acids and phytosterols. Se nutritional status determined by quantification of various biomarkers is more advantageous because it allows to infer the Se intake more reliably. In individuals with adequate Se status, Se intake can be estimated by concentrations plasma Se. Among the biomarkers, the Selenoprotein P (SEPP) and Plasma Glutathione Peroxidase (GPx3) constitute approximately 50% to 20% of plasma Se, respectively. Being sensitive to changes in Se intake SEPP is considered an excellent marker of Se intake, especially in individuals with marginal to low Se status, such southern and southeastern population of Brazil. The plateau of GPx3 activity was used to determine the EAR (Estimate Average Requirement,) based on only two intervention studies. There are no reports in the literature of Brazilian studies using Sepp and GPx3 activity as biomarkers of Se status, moreover no work that used Brazil nut supplementation used SEPP and GPx3 as biomarkers. The effect of Se supplementation was evaluated in studies conducted in animal and humans models, and as different responses were observed, genetic variability becomes increasingly evident. Currently, two polymorphisms in SEPP1 gene were proved to have functional consequences. OBJETIVOS: To determine plasma concentrations of Sepp and GPx3 and relate the genetic profile with biomarker concentrations in response to supplementation with Brazil-Brazil. METHODOLOGY: This project will use 130 samples already collected as part of the regular doctoral project . The population was recruited in the University of São Paulo. The volunteers took one Brazil nut for eight weeks and further 8 weeks without it. Five blood sampling each volunteer were conducted once a month. The SEPP concentrations will be determined in plasma by immunoassay using two monoclonal antibodies. Briefly, each antibody recognizes a specific binding site in the N-terminal tail of selenoprotein P. Standard Curves 0.15 to 5 ng / ml will be constructed using purified human selenoprotein P. Plasma GPx3 activity will be performed according to the method proposed by Paglia and Valentine, modified for the specific enzyme. The method is based on the reduction of hydrogen peroxide catalyzed by GPx, using glutathione as the reducing agent. The concentration of glutathione is maintained by the addition of glutathione reductase and NADPH which converts oxidized glutathione in its reduced form.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DONADIO, JANAINA L. S.; DUARTE, GRAZIELA B. S.; BOREL, PATRICK; COZZOLINO, SILVIA M. F.; ROGERO, MARCELO M.. The influence of nutrigenetics on biomarkers of selenium nutritional status. NUTRITION REVIEWS, v. 79, n. 11, p. 1259-1273, . (15/10146-8, 11/17720-0)
DONADIO, JANAINA L. S.; ROGERO, MARCELO M.; GUERRA-SHINOHARA, ELVIRA M.; BARBOSA, JR., FERNANDO; DESMARCHELIER, CHARLES; BOREL, PATRICK; SNEDDON, ALAN A.; HESKETH, JOHN E.; COZZOLINO, SILVIA M. F.. Genetic variants in selenoprotein genes modulate biomarkers of selenium status in response to Brazil nut supplementation (the SU.BRA.NUT study). Clinical Nutrition, v. 38, n. 2, p. 539-548, . (11/17720-0, 15/10146-8)

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