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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)798-805
Number of pages8
JournalRedox Biology
StatePublished - Aug 1 2017

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry


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