Influence of Genetic Variations in Selenoprotein Genes on the Pattern of Gene Expression after Supplementation with Brazil Nuts

Janaina L S Donadio, Marcelo M Rogero, Simon Cockell, John Hesketh, Silvia M F Cozzolino, Janaina L S Donadio, Marcelo M Rogero, Simon Cockell, John Hesketh, Silvia M F Cozzolino

Abstract

Selenium (Se) is an essential micronutrient for human health. Its beneficial effects are exerted by selenoproteins, which can be quantified in blood and used as molecular biomarkers of Se status. We hypothesize that the presence of genetic polymorphisms in selenoprotein genes may: (1) influence the gene expression of specific selenoproteins and (2) influence the pattern of global gene expression after Brazil nut supplementation. The study was conducted with 130 healthy volunteers in Sao Paulo, Brazil, who consumed one Brazil nut (300 μg/Se) a day for eight weeks. Gene expression of GPX1 and SELENOP and genotyping were measured by real-time PCR using TaqMan Assays. Global gene expression was assessed by microarray using Illumina HumanHT-12 v4 BeadChips. Brazil nut supplementation significantly increased GPX1 mRNA expression only in subjects with CC genotype at rs1050450 (p < 0.05). SELENOP mRNA expression was significantly higher in A-carriers at rs7579 either before or after supplementation (p < 0.05). Genotype for rs713041 in GPX4 affected the pattern of blood cell global gene expression. Genetic variations in selenoprotein genes modulated both GPX1 and SELENOP selenoprotein gene expression and global gene expression in response to Brazil nut supplementation.

Keywords: SNPs; microarray; micronutrient; polymorphisms; transcriptomics.

Conflict of interest statement

The authors declared no conflict of interests.

Figures

Figure 1
Figure 1
Intervention protocol of the Supplementation with Brazil Nuts study (SU.BRA.NUT) Biological sample collection for the microarray experiment is shown. CC indicates common genotype and TT indicates rare genotype for rs713041 in GPX4 gene.
Figure 2
Figure 2
Selenoprotein expression in response to Brazil nut supplementation in previously genotyped volunteers. (a) GPX1 mRNA expression as a function of genotype for rs1050450; (b) SELENOP mRNA expression as a function of genotype for rs7579. * p < 0.05, Mann–Whitney test. ** p < 0.05, Wilcoxon test.
Figure 3
Figure 3
Volcano plots for the four experimental conditions investigated in the SU.BRA.NUT study. (a) Before supplementation comparing the genotypes CC × TT; (b) after supplementation comparing the genotypes CC × TT; (c) effect of the supplementation in the CC genotype and (d) effect of the supplementation in TT genotype.
Figure 4
Figure 4
Heatmap showing patterns of differential expression in TT and CC genotype after Brazil nut supplementation. Red indicates genes with higher expression levels and blue genes with lower expression levels.

References

    1. Bolling B.W., Chen C.-Y.O., McKay D.L., Blumberg J.B. Tree nut phytochemicals: Composition, antioxidant capacity, bioactivity, impact factors. A systematic review of almonds, Brazils, cashews, hazelnuts, macadamias, pecans, pine nuts, pistachios and walnuts. Nutr. Res. Rev. 2011;24:244–275. doi: 10.1017/S095442241100014X.
    1. Alasalvar C., Bolling B.W. Review of nut phytochemicals, fat-soluble bioactives, antioxidant components and health effects. Br. J. Nutr. 2015;113:S68–S78. doi: 10.1017/S0007114514003729.
    1. O’Neil C.E., Fulgoni V.L., Nicklas T.A. Tree Nut consumption is associated with better adiposity measures and cardiovascular and metabolic syndrome health risk factors in U.S. adults: NHANES 2005–2010. Nutr. J. 2015;14:64–71. doi: 10.1186/s12937-015-0052-x.
    1. Dumont E., De Pauw L., Vanhaecke F., Cornelis R. Speciation of Se in Bertholletia excelsa (Brazil nut): A hard nut to crack? Food Chem. 2006;95:684–692. doi: 10.1016/j.foodchem.2005.04.004.
    1. Thomson C.D., Chisholm A., Mclachlan S.K., Campbell J.M. Brazil nuts: An effective way to improve selenium status. Am. J. Clin. Nutr. 2008;87:379–384.
    1. Cardoso B.R., Apolinário D., Bandeira V.S., Busse A.L., Magaldi R.M., Jacob-Filho W., Cozzolino S.M.F. Effects of Brazil nut consumption on selenium status and cognitive performance in older adults with mild-cognitive impairment: A randomized controlled pilot trial. Eur. J. Nutr. 2016;55:107–116. doi: 10.1007/s00394-014-0829-2.
    1. Cominetti C., de Bortoli M.C., Garrido A.B., Cozzolino S.M.F. Brazilian nut consumption improves selenium status and glutathione peroxidase activity and reduces atherogenic risk in obese women. Nutr. Res. 2012;32:403–407. doi: 10.1016/j.nutres.2012.05.005.
    1. Kryukov G.V., Castellano S., Novoselov S.V., Lobanov A.V., Zehtab O., Guigó R., Gladyshev V.N. Characterization of mammalian selenoproteomes. Science. 2003;300:1439–1443. doi: 10.1126/science.1083516.
    1. Rayman M.P. Selenium and human health. Lancet. 2012;379:1256–1268. doi: 10.1016/S0140-6736(11)61452-9.
    1. Labunskyy V.M., Hatfield D.L., Gladyshev V.N. Selenoproteins: Molecular Pathways and Physiological Roles. Physiol. Rev. 2014;94:739–777. doi: 10.1152/physrev.00039.2013.
    1. Schomburg L., Schweizer U. Hierarchical regulation of selenoprotein expression and sex-specific effects of selenium. Biochim. Biophys. Acta. 2009;1790:1453–1462. doi: 10.1016/j.bbagen.2009.03.015.
    1. Sunde R.A., Raines A.M., Barnes K.M., Evenson J.K. Selenium status highly regulates selenoprotein mRNA levels for only a subset of the selenoproteins in the selenoproteome. Biosci. Rep. 2009;29:329–338. doi: 10.1042/BSR20080146.
    1. Ravn-Haren G., Bügel S., Krath B.N., Hoac T., Stagsted J., Jørgensen K., Bresson J.R., Larsen E.H., Dragsted L.O. A short-term intervention trial with selenate, selenium-enriched yeast and selenium-enriched milk: Effects on oxidative defence regulation. Br. J. Nutr. 2008;99:883–892. doi: 10.1017/S0007114507825153.
    1. Ravn-Haren G., Krath B.N., Overvad K., Cold S., Moesgaard S., Larsen E.H., Dragsted L.O. Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) pilot study. Br. J. Nutr. 2008;99:1190–1198. doi: 10.1017/S0007114507882948.
    1. Sunde R.A., Paterson E., Evenson J.K., Barnes K.M., Lovegrove J.A., Gordon M.H. Longitudinal selenium status in healthy British adults: Assessment using biochemical and molecular biomarkers. Br. J. Nutr. 2008;99(Suppl. 3):S37–S47. doi: 10.1017/S0007114508006831.
    1. Pagmantidis V., Méplan C., Van Schothorst E.M., Keijer J., Hesketh J.E. Supplementation of healthy volunteers with nutritionally relevant amounts of selenium increases the expression of lymphocyte protein biosynthesis genes. Am. J. Clin. Nutr. 2008;87:181–189.
    1. Cardoso B.R., Busse A.L., Hare D.J., Cominetti C., Horst M.A., Mccoll G., Magaldi R.M., Jacob-Filho W., Cozzolino S.M.F. Pro198Leu polymorphism affects the selenium status and GPx activity in response to Brazil nut intake. Food Funct. 2016;9:825–833. doi: 10.1039/C5FO01270H.
    1. Hesketh J., Méplan C. Transcriptomics and functional genetic polymorphisms as biomarkers of micronutrient function: Focus on selenium as an exemplar. Proc. Nutr. Soc. 2011;70:365–373. doi: 10.1017/S0029665111000115.
    1. Méplan C., Crosley L.K., Nicol F., Beckett G.J., Howie A.F., Hill K.E., Horgan G., Mathers J.C., Arthur J.R., Hesketh J.E. Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study) FASEB J. 2007;21:3063–3074. doi: 10.1096/fj.07-8166com.
    1. Méplan C., Crosley L.K., Nicol F., Horgan G.W., Mathers J.C., Arthur J.R., Hesketh J.E. Functional effects of a common single-nucleotide polymorphism (GPX4c718t) in the glutathione peroxidase 4 gene: Interaction with sex. Am. J. Clin. Nutr. 2008;87:1019–1027.
    1. Combs G.F., Jackson M.I., Watts J.C., Johnson L.K., Zeng H., Idso J., Schomburg L., Hoeg A., Hoefig C.S., Chiang E.C., et al. Differential responses to selenomethionine supplementation by sex and genotype in healthy adults. Br. J. Nutr. 2012;107:1514–1525. doi: 10.1017/S0007114511004715.
    1. Jablonska E., Gromadzinska J., Reszka E., Wasowicz W., Sobala W., Szeszenia-Dabrowska N., Boffetta P. Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans. Eur. J. Nutr. 2009;48:383–386. doi: 10.1007/s00394-009-0023-0.
    1. Bermano G., Pagmantidis V., Holloway N., Kadri S., Mowat N.A.G., Shiel R.S., Arthur J.R., Mathers J.C., Daly A.K., Broom J., et al. Evidence that a polymorphism within the 3′UTR of glutathione peroxidase 4 is functional and is associated with susceptibility to colorectal cancer. Genes Nutr. 2007;2:225–232. doi: 10.1007/s12263-007-0052-3.
    1. Donadio J.L.S., Rogero M.M., Guerra‑shinohara E.M., Desmarchelier C., Borel P., Cozzolino S.M.F. SEPP1 polymorphisms modulate serum glucose and lipid response to Brazil nut supplementation. Eur. J. Nutr. 2017:1–10. doi: 10.1007/s00394-017-1470-7.
    1. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–408. doi: 10.1006/meth.2001.1262.
    1. Ritchie M.E., Dunning M.J., Smith M.L., Shi W., Lynch A.G. BeadArray Expression Analysis Using Bioconductor. PLoS Comput. Biol. 2011;7:e1002276. doi: 10.1371/journal.pcbi.1002276.
    1. Subramanian A., Tamayo P., Mootha V.K., Mukherjee S., Ebert B.L. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide. Proc. Natl. Acad. Sci. USA. 2005;102:15545–15550. doi: 10.1073/pnas.0506580102.
    1. Cole-Ezea P., Swan D., Shanley D., Hesketh J. Glutathione peroxidase 4 has a major role in protecting mitochondria from oxidative damage and maintaining oxidative phosphorylation complexes in gut epithelial cells. Free Radic. Biol. Med. 2012;53:488–497. doi: 10.1016/j.freeradbiomed.2012.05.029.
    1. Hamanishi T., Furuta H., Kato H., Doi A., Tamai M., Shimomura H., Sakagashira S., Nishi M., Sasaki H., Sanke T., et al. Functional variants in the glutathione peroxidase-1 (GPx-1) gene are associated with increased intima-media thickness of carotid arteries and risk of macrovascular diseases in Japanese type 2 diabetic patients. Diabetes. 2004;53:2455–2460. doi: 10.2337/diabetes.53.9.2455.
    1. Hansen R.D., Krath B.N., Frederiksen K., Tjønneland A., Overvad K., Roswall N., Loft S., Dragsted L.O., Vogel U., Raaschou-Nielsen O. GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer. Mutat. Res. 2009;664:13–19. doi: 10.1016/j.mrfmmm.2009.01.009.
    1. Méplan C., Nicol F., Burtle B.T., Crosley L.K., Arthur J.R., Mathers J.C., Hesketh J.E. Relative abundance of selenoprotein P isoforms in human plasma depends on genotype, se intake, and cancer status. Antioxid. Redox Signal. 2009;11:2631–2640. doi: 10.1089/ars.2009.2533.
    1. Crosley L.K., Bashir S., Nicol F., Arthur J.R., Hesketh J.E., Sneddon A.A. The single-nucleotide polymorphism (GPX4c718t) in the glutathione peroxidase 4 gene influences endothelial cell function: Interaction with selenium and fatty acids. Mol. Nutr. Food Res. 2013;57:2185–2194. doi: 10.1002/mnfr.201300216.
    1. Hawkes W.C., Richter D., Alkan Z. Dietary selenium supplementation and whole blood gene expression in healthy North American men. Biol. Trace Elem. Res. 2013;155:201–208. doi: 10.1007/s12011-013-9786-5.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera