Influence of Gender and SNPs in GPX1 Gene on Biomarkers of Selenium Status in Healthy Brazilians

Janaina L S Donadio, Elvira M Guerra-Shinohara, Marcelo M Rogero, Silvia M F Cozzolino, Janaina L S Donadio, Elvira M Guerra-Shinohara, Marcelo M Rogero, Silvia M F Cozzolino

Abstract

Selenium (Se) status varies worldwide as a result of natural variation of Se content in soils, dietary pattern, and the presence of SNPs. Further, Se status in Brazilians and its relationship between genetic variation and Se biomarkers is unknown. This work investigated the association between SNPs in glutathione peroxidase genes and biomarkers of Se status in healthy Brazilians. The study was conducted in 116 healthy adults in São Paulo, Brazil. Plasma and erythrocyte Se were measured by HGFAAS. Erythrocyte GPx (eGPx) activity was measured spectrometrically in a biochemical analyzer. Genotypes were determined by real-time PCR using Taqman(®) Assays. eGPx activity was higher in females compared with males. Lower erythrocyte Se concentrations were found in heterozygous GC carriers for GPX1 rs8179169. eGPx activity was higher in females with the common genotypes, except for rs8179169. GC carriers for rs8179169 had lower erythrocyte Se in both genders, and only male carriers of the variant alleles of both rs1050450 and rs1800668 had higher eGPx activity. In conclusion, the genotype for SNPs in GPX1 and gender affected biomarkers of Se status in this pilot study with healthy Brazilians.

Keywords: biomarkers; glutathione peroxidase (GPx); selenium (Se); single nucleotide polymorphisms (SNPs).

References

    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. Papp L.V., Lu J., Holmgren A., Khanna K.K. From selenium to selenoproteins: Synthesis, Identity, and Their Role in Human Health. Antioxid. Redox Signal. 2007;9:775–806. doi: 10.1089/ars.2007.1528.
    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. Takebe G., Yarimizu J., Saito Y., Hayashi T., Nakamura H., Yodoi J., Nagasawa S., Takahashi K. A comparative study on the hydroperoxide and thiol specificity of the glutathione peroxidase family and selenoprotein P. J. Biol. Chem. 2002;277:41254–41258. doi: 10.1074/jbc.M202773200.
    1. Traulsen H., Steinbrenner H., Buchczyk D.P., Klotz L.O., Sies H. Selenoprotein P protects low-density lipoprotein against oxidation. Free Radic. Res. 2004;38:123–128. doi: 10.1080/10715760320001634852.
    1. McKenzie R.C., Rafferty T.S., Beckett G.J. Selenium: An Essential Element for Immune Function. Immunol. Today. 1998;19:342–345. doi: 10.1016/S0167-5699(98)01294-8.
    1. Duntas L.H. Selenium and inflammation: Underlying Anti-Inflammatory Mechanisms. Horm. Metab. Res. 2009;41:443–447. doi: 10.1055/s-0029-1220724.
    1. Rayman M.P. Selenoproteins and human health: Insights from Epidemiological Data. Biochim. Biophys. Acta Gen. Subj. 2009;1790:1533–1540. doi: 10.1016/j.bbagen.2009.03.014.
    1. Stranges S., Navas-Acien A., Rayman M.P., Guallar E. Selenium status and cardiometabolic health: State of the Evidence. Nutr. Metab. Cardiovasc. Dis. 2010;20:754–760. doi: 10.1016/j.numecd.2010.10.001.
    1. Oldfield J.E. Selenium World Atlas. 2nd ed. Selenium-Tellurium Development Association; Grimbergen, Belgium: 2002. p. 59.
    1. Combs G.F. Selenium in global food systems. Br. J. Nutr. 2001;85:81. doi: 10.1079/BJN2000280.
    1. Hooper L., Ashton K., Harvey L.J., Decsi T., Fairweather-Tait S.J. Assessing potential biomarkers of micronutrient status by using a systematic review methodology: Methods. Am. J. Clin. Nutr. 2009;89:1953S–1959S. doi: 10.3945/ajcn.2009.27230A.
    1. Combs G.F. Biomarkers of Selenium Status. Nutrients. 2015;7:2209–2236. doi: 10.3390/nu7042209.
    1. Thomson C.D. Assessment of requirements for selenium and adequacy of selenium status: A Review. Eur. J. Clin. Nutr. 2004;58:391–402. doi: 10.1038/sj.ejcn.1601800.
    1. Combs G.F., Watts J.C., Jackson M.I., Johnson L.K., Zeng H., Scheett A.J., Uthus E.O., Schomburg L., Hoeg A., Hoefig C.S., et al. Determinants of selenium status in healthy adults. Nutr. J. 2011;10:81. doi: 10.1186/1475-2891-10-75.
    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. 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. 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. Villette S., Kyle J.M., Brown K.M., Pickard K., Milne J.S., Nicol F., Arthur J.R., Hesketh J.E. A novel single nucleotide polymorphism in the 3’ untranslated region of human glutathione peroxidase 4 influences lipoxygenase metabolism. Blood Cells. Mol. Dis. 2002;29:174–178. doi: 10.1006/bcmd.2002.0556.
    1. Bermano G., Pagmantidis V., Holloway N., Kadri S., Mowat N.A., Shiel N.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. Hao D.Q., Xie G.H., Zhang Y.M., Tian G.J. Determination of serum selenium by hydride generation flame atomic absorption spectrometry. Talanta. 1996;43:595–600. doi: 10.1016/0039-9140(95)01786-0.
    1. National Center for Biotechnology Information. [(accessed on 20 March 2010)]; Available online:
    1. Ramensky V., Bork P., Sunyaev S. Human non-synonymous SNPs: Server and survey. Nucleic Acids Res. 2002;30:3894–3900. doi: 10.1093/nar/gkf493.
    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. Takata Y., King I.B., Lampe J.W., Burk R.F., Hill K.E., Santella R.M., Kristal A.R., Duggan D.J., Vaughan T.L., Peters U. Genetic Variation in GPX1 Is Associated with GPX1 Activity in a Comprehensive Analysis of Genetic Variations in Selenoenzyme Genes and Their Activity and Oxidative Stress in Humans. J. Nutr. 2012;142:419–426. doi: 10.3945/jn.111.151845.
    1. Karunasinghe N., Han D.Y., Zhu S., Yu J., Lange K., Duan H., Medhora R., Singh N., Kan J., Alzaher W., et al. Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: Relationship to Markers of Oxidative Stress in Men from Auckland, New Zealand. Genes Nutr. 2012;7:179–190. doi: 10.1007/s12263-011-0259-1.
    1. Ashton K., Hooper L., Harvey L.J., Hurst R., Casgrain A., Fairweather-Tait S.J. Methods of assessment of selenium status in humans: A Systematic Review. Am. J. Clin. Nutr. 2009;89:2025S–2039S. doi: 10.3945/ajcn.2009.27230F.
    1. Bastaki M., Huen K., Manzanillo P., Chande N., Chen C., Balmes J.R., Tager I.B., Holland N. Genotype-activity relationship for Mn-superoxide dismutase, glutathione peroxidase 1 and catalase in humans. Pharmacogenet. Genomics. 2006;16:279–286. doi: 10.1097/01.fpc.0000199498.08725.9c.
    1. Suzen H.S., Gucyener E., Sakalli O., Uckun Z., Kose G., Ustel D., Duydu Y. CAT C-262T and GPX1 Pro198Leu polymorphisms in a Turkish population. Mol. Biol. Rep. 2010;37:87–92. doi: 10.1007/s11033-009-9540-4.
    1. Forsberg L., de Faire U., Marklund S.L., Andersson P.M., Stegmayr B., Morgenstern R. Phenotype determination of a common Pro-Leu polymorphism in human glutathione peroxidase 1. Blood Cells. Mol. Dis. 2000;26:423–426. doi: 10.1006/bcmd.2000.0325.
    1. Méplan C., Dragsted L.O., Ravn-Haren G., Tjønneland A., Vogel U., Hesketh J. Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk. PLoS ONE. 2013;8:81
    1. Cardoso B.R., Ong T.P., Jacob-Filho W., Jaluul O., Freitas M.I.A., Cominetti C., Cozzolino S.M.F. Glutathione peroxidase 1 pro198leu polymorphism in Brazilian Alzheimer’s disease patients: Relations to the Enzyme Activity and to Selenium Status. J. Nutrigenet. Nutrigenomics. 2012;5:72–80. doi: 10.1159/000338682.
    1. Cominetti C., de Bortoli M.C., Purgatto E., Ong T.P., Moreno F.S., Garrido A.B., Cozzolino S.M.F. Associations between glutathione peroxidase-1 Pro198Leu polymorphism, selenium status, and DNA damage levels in obese women after consumption of Brazil nuts. Nutrition. 2011;27:891–896. doi: 10.1016/j.nut.2010.09.003.
    1. Miranda-Vilela A.L., Alves P.C., Akimoto A.K., Lordelo G.S., Gonçalves C.A., Grisolia C.K., Klautau-Guimarães M.N. Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: A Quasi-Experimental Study. Environ. Health. 2010;9:81. doi: 10.1186/1476-069X-9-21.
    1. De Hiragi C.O., Miranda-Vilela A.L., Rocha D.M.S., de Oliveira S.F., Hatagima A., de Klautau-Guimarães M.N. Superoxide dismutase, catalase, glutathione peroxidase and gluthatione s-transferases M1 and T1 gene polymorphisms in three brazilian population groups. Genet. Mol. Biol. 2011;34:11–18.
    1. Iida R., Tsubota E., Yuasa I., Takeshita H., Yasuda T. Simultaneous genotyping of 11 non-synonymous SNPs in the 4 glutathione peroxidase genes using the multiplex single base extension method. Clin. Chim. Acta. 2009;402:79–82. doi: 10.1016/j.cca.2008.12.027.
    1. Massafra C., Gioia D., De Felice C., Muscettola M., Longini M., Buonocore G. Gender related differences in erythrocyte glutathione peroxidase activity in healthy subjects. Clin. Endocrinol. 2002;57:663–667. doi: 10.1046/j.1365-2265.2002.01657.x.
    1. Ravn-Haren G., Olsen A., Tjønneland A., Dragsted L.O., Nexø B.A., Wallin H., Overvad K., Raaschou-Nielsen O., Vogel U. Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study. Carcinogenesis. 2006;27:820–825. doi: 10.1093/carcin/bgi267.
    1. Arsova-Sarafinovska Z., Matevska N., Eken A., Petrovski D., Banev S., Dzikova S., Georgiev V., Sikole A., Erdem O., Sayal A., et al. Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk. Int. Urol. Nephrol. 2009;41:63–70. doi: 10.1007/s11255-008-9407-y.
    1. Pin Z., Goldberg M., Herman L., Lee B.S., Hengbing W., Brown R.L., Foster C.B., Peters U., Diamond A.M. Molecular consequences of genetic variations in the glutathione peroxidase 1 selenoenzyme. Cancer Res. 2009;69:8183–8190.
    1. Cengiz M., Bayoglu B., Alansal N.O., Cengiz S., Dirican A., Kocabasoglu N. Pro198Leu polymorphism in the oxidative stress gene, glutathione peroxidase-1, is associated with a gender-specific risk for panic disorder. Int. J. Psychiatry Clin. Pract. 2015;19:201–207. doi: 10.3109/13651501.2015.1016973.
    1. Burk R.F., Hill K.E. Selenoprotein P-Expression, functions, and roles in mammals. Biochim. Biophys. Acta Gen. Subj. 2009;1790:1441–1447. doi: 10.1016/j.bbagen.2009.03.026.
    1. Ratnasinghe D., Tangrea J.A., Andersen M.R., Barrett M.J., Virtamo J., Taylor P.R., Albanes D. Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk. Cancer Res. 2000;60:6381–6383.
    1. Ichimura Y., Habuchi T., Tsuchiya N., Wang L., Oyama C., Sato K., Nishiyama H., Ogawa O., Kato T. Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant. J. Urol. 2004;172:728–732. doi: 10.1097/01.ju.0000130942.40597.9d.
    1. Zhao H., Liang D., Grossman H.B., Wu X. Glutathione peroxidase 1 gene polymorphism and risk of recurrence in patients with superficial bladder cancer. Urology. 2005;66:769–774. doi: 10.1016/j.urology.2005.04.033.
    1. Karunasinghe N., Han D.Y., Goudie M., Zhu S., Bishop K., Wang A., Duan H., Lange K., Ko S., Medhora R., et al. Prostate disease risk factors among a New Zealand cohort. J. Nutrigenet. Nutrigenomics. 2012;5:339–351. doi: 10.1159/000346279.
    1. Udler M., Maia A.T., Cebrian A., Brown C., Greenberg D., Shah M., Caldas C., Dunning A., Easton D., Ponder B., et al. Common germline genetic variation in antioxidant defense genes and survival after diagnosis of breast cancer. J. Clin. Oncol. 2007;25:3015–3023. doi: 10.1200/JCO.2006.10.0099.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj