title: Plasma selenium levels and oxidative stress biomarkers: a gene-environment interaction population-based study.
abstract: The role of selenium exposure in preventing chronic disease is controversial, especially in selenium-repleted populations. At high concentrations, selenium exposure may increase oxidative stress. Studies evaluating the interaction of genetic variation in genes involved in oxidative stress pathways and selenium are scarce. We evaluated the cross-sectional association of plasma selenium concentrations with oxidative stress levels, measured as oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8-oxo-7,8-dihydroguanine (8-oxo-dG) in urine, and the interacting role of genetic variation in oxidative stress candidate genes, in a representative sample of 1445 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.76 µg/L. In fully adjusted models the geometric mean ratios for oxidative stress biomarker levels comparing the highest to the lowest quintiles of plasma selenium levels were 0.61 (0.50-0.76) for GSSG/GSH, 0.89 (0.79-1.00) for MDA, and 1.06 (0.96-1.18) for 8-oxo-dG. We observed nonlinear dose-responses of selenium exposure and oxidative stress biomarkers, with plasma selenium concentrations above ~110 μg/L being positively associated with 8-oxo-dG, but inversely associated with GSSG/GSH and MDA. In addition, we identified potential risk genotypes associated with increased levels of oxidative stress markers with high selenium levels. Our findings support that high selenium levels increase oxidative stress in some biological processes. More studies are needed to disentangle the complexity of selenium biology and the relevance of potential gene-selenium interactions in relation to health outcomes in human populations.
authors.affiliation: Genotyping and Genetic Diagnosis Unit, Institute for Biomedical Research INCLIVA, Valencia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Galan-Chilet
authors.affiliation: Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research INCLIVA, Valencia, Spain; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. Electronic address: maria.tellez@uv.es.
authors.forename: Maria
authors.initials: M
authors.lastname: Tellez-Plaza
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.affiliation: Genotyping and Genetic Diagnosis Unit, Institute for Biomedical Research INCLIVA, Valencia, Spain.
authors.forename: Griselda
authors.initials: G
authors.lastname: De Marco
authors.affiliation: Department of Internal Medicine, Hospital Universitario Rio Hortega, Valladolid, Spain.
authors.forename: Raul
authors.initials: R
authors.lastname: Lopez-Izquierdo
authors.affiliation: Department of Internal Medicine, Hospital Universitario Rio Hortega, Valladolid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonzalez-Manzano
authors.affiliation: CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Minister of Health, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Carmen Tormos
authors.affiliation: Department of Endocrinology and Nutrition, Biomedical Research Institute of Malaga (IBIMA), Hospital Regional Universitario de Malaga, Malaga, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain.
authors.forename: Gracia M
authors.initials: GM
authors.lastname: Martin-Nuñez
authors.affiliation: Department of Endocrinology and Nutrition, Biomedical Research Institute of Malaga (IBIMA), Hospital Regional Universitario de Malaga, Malaga, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Rojo-Martinez
authors.affiliation: CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Minister of Health, Madrid, Spain; Department of Biochemistry and Molecular Biology, School of Medicine, University of Valencia, Spain; Service of Clinical Analysis-CDBI; Hospital General Universitario de Valencia (HGUV) Valencia, Spain.
authors.forename: Guillermo T
authors.initials: GT
authors.lastname: Saez
authors.affiliation: Department of Internal Medicine, Hospital Universitario Rio Hortega, Valladolid, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Martín-Escudero
authors.affiliation: Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research INCLIVA, Valencia, Spain; CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Minister of Health, Madrid, Spain; Department of Internal Medicine, Hospital Clínico de Valencia, Valencia, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Redon
authors.affiliation: Genotyping and Genetic Diagnosis Unit, Institute for Biomedical Research INCLIVA, Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Javier Chaves
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000652:urine; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000652:urine; D008875:Middle Aged; D018384:Oxidative Stress; D012643:Selenium / Q000097:blood*; D013030:Spain; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione; D012643:Selenium; D019803:Glutathione Disulfide
keywords: Gene–environment interaction; Oxidative stress; Population based; Selenium