Abstract
Mechanistic data have revealed a key role for selenium (Se) and selenoproteins in biological pathways known to be altered in multifactorial diseases, such as cellular maintenance, response to oxidative stress and correct protein folding. Although epidemiological studies indicate that low Se intake is linked to increased risk for various chronic diseases, supplementation trials have given confusing outcomes, suggesting that additional genetic factors could affect the relationship between Se and health. Genetic data support this hypothesis, as risk for several chronic diseases, in particular cancer, was linked to a number of single nucleotide polymorphisms (SNP) altering Se metabolism, selenoprotein synthesis or activity. Interactions between SNPs in selenoprotein genes, SNPs in related molecular pathways and biomarkers of Se status were found to further modulate the genetic risk carried by the SNPs. Taken together, nutritional genomics approaches uncovered the potential implication of some selenoproteins as well as the influence of complex interactions between genetic variants and Se status in the aetiology of several chronic diseases. This review discusses the results from these genetic associations in the context of selenoprotein functions and epidemiological investigations and emphasises the need to assess in future studies the combined contribution of Se status, environmental stress, and multiple or individual SNPs to disease risk.
Highlights
The relationship between health and nutrition has been recognized for a long time; it was not until the development of high-throughput technologies that followed the sequencing of the human genome that the dynamics of this relationship could be unveiled, which was found to be influenced by the interactions between individual genetic makeup and environmental factors such as dietary components
Alteration of selenoprotein synthesis or activity has been linked to development of chronic diseases such as cancer [59]
The application of Nutritional Genomics approaches to Se biology has highlighted that genetic variants in selenoprotein and Se-related genes affect the risk for multifactorial diseases, uncovering potential roles for particular selenoproteins in specific disease or tissue function
Summary
The relationship between health and nutrition has been recognized for a long time; it was not until the development of high-throughput technologies that followed the sequencing of the human genome that the dynamics of this relationship could be unveiled, which was found to be influenced by the interactions between individual genetic makeup and environmental factors such as dietary components. The applications of these technologies to nutrition research led to the development of nutritional genomics which studies both the effect of an individual’s genetic makeup on the response to nutrients (nutrigenetics) and the modulation of gene expression by nutritional compounds (nutrigenomics). This review discusses the relationship between diseases and genetic variations in selenoprotein genes with an emphasis on the function of selenoproteins and factors that governs Se homeostasis
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