A gene-environment interaction analysis of plasma selenium with prevalent and incident diabetes: The Hortega study
Inmaculada Galan-Chilet,
Maria Grau-Perez,
Griselda De Marco,
Eliseo Guallar,
Juan Carlos Martin-Escudero,
Alejandro Dominguez-Lucas,
Isabel Gonzalez-Manzano,
Raul Lopez-Izquierdo,
Laisa Socorro Briongos-Figuero,
Josep Redon,
Felipe Javier Chaves,
Maria Tellez-Plaza
Affiliations
Inmaculada Galan-Chilet
Genomic and Genetic Diagnosis Unit, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Valencia, Spain
Maria Grau-Perez
Area of Cardiometabolic and Renal Risk, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Valencia, Spain; Department of Environmental Health Sciences, Columbia University, New York, NY, USA; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Griselda De Marco
Genomic and Genetic Diagnosis Unit, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Valencia, Spain
Eliseo Guallar
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Juan Carlos Martin-Escudero
Department of Internal Medicine, University Hospital Rio Hortega, Valladolid, Spain
Alejandro Dominguez-Lucas
Area of Cardiometabolic and Renal Risk, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Valencia, Spain
Isabel Gonzalez-Manzano
Department of Internal Medicine, University Hospital Rio Hortega, Valladolid, Spain
Raul Lopez-Izquierdo
Department of Internal Medicine, University Hospital Rio Hortega, Valladolid, Spain
Laisa Socorro Briongos-Figuero
Department of Internal Medicine, University Hospital Rio Hortega, Valladolid, Spain
Josep Redon
Area of Cardiometabolic and Renal Risk, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Valencia, Spain; CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain; Department of Internal Medicine, University Hospital Clinic of Valencia, Valencia, Spain
Felipe Javier Chaves
Genomic and Genetic Diagnosis Unit, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Institute of Health Carlos III, Madrid, Spain; Correspondence to: Biomedical Research Institute INCLIVA, Av. Menendez Pidal 4 accesorio, 46010 Valencia, Spain.
Maria Tellez-Plaza
Area of Cardiometabolic and Renal Risk, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Valencia, Spain; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Background: Selenium and single-nucleotide-polymorphisms in selenoprotein genes have been associated to diabetes. However, the interaction of selenium with genetic variation in diabetes and oxidative stress-related genes has not been evaluated as a potential determinant of diabetes risk. Methods: We evaluated the cross-sectional and prospective associations of plasma selenium concentrations with type 2 diabetes, and the interaction of selenium concentrations with genetic variation in candidate polymorphisms, in a representative sample of 1452 men and women aged 18–85 years from Spain. Results: The geometric mean of plasma selenium levels in the study sample was 84.2 µg/L. 120 participants had diabetes at baseline. Among diabetes-free participants who were not lost during the follow-up (N=1234), 75 developed diabetes over time. The multivariable adjusted odds ratios (95% confidence interval) for diabetes prevalence comparing the second and third to the first tertiles of plasma selenium levels were 1.80 (1.03, 3.14) and 1.97 (1.14, 3.41), respectively. The corresponding hazard ratios (95% CI) for diabetes incidence were 1.76 (0.96, 3.22) and 1.80 (0.98, 3.31), respectively. In addition, we observed significant interactions between selenium and polymorphisms in PPARGC1A, and in genes encoding mitochondrial proteins, such as BCS1L and SDHA, and suggestive interactions of selenium with other genes related to selenoproteins and redox metabolism. Conclusions: Plasma selenium was positively associated with prevalent and incident diabetes. While the statistical interactions of selenium with polymorphisms involved in regulation of redox and insulin signaling pathways provide biological plausibility to the positive associations of selenium with diabetes, further research is needed to elucidate the causal pathways underlying these associations.
