Micronutrients are essential for optimal human health. However, in some cases,
raising intake by supplementation has not proven to be beneficial and there is
even some evidence that supplementation may increase disease risk, highlighting
the importance of assessing the functional status of micronutrients. Techniques
such as gene microarrays and single-nucleotide polymorphism analysis have the
potential to examine effects of micronutrient intake on patterns of gene
expression and inter-individual variation in micronutrient metabolism. Recent
genomic research related to selenium (Se) provides examples illustrating how
studies of functional single-nucleotide polymorphism and gene expression
patterns can reveal novel biomarkers of micronutrient function. Both in
vitro and in vivo experiments show that there are
functionally relevant polymorphisms in genes encoding glutathione peroxidases 1,
3 and 4, selenoprotein P, selenoprotein S and the 15 kDa selenoprotein. Disease
association studies investigating these gene variants have so far been
relatively small but an association of a polymorphism in the selenoprotein S
gene with colorectal cancer risk has been replicated in two distinct
populations. Future disease association studies should examine effects of
multiple variants in combination with nutritional status. Gene microarray
studies indicate that changes in Se intake alter expression of components of
inflammatory, stress response and translation pathways. Our hypothesis is that
Se intake and genetic factors have linked effects on stress response,
inflammation and apoptotic pathways. Combining such data in a systems biology
approach has the potential to identify both biomarkers of micronutrients status
and sub-group populations at particular risk.
Combined single nucleotide polymorphism-based genomic mapping and global gene expression profiling identifies novel chromosomal imbalances, mechanisms and candidate genes important in the pathogenesis of T-cell prolymphocytic leukemia with inv(14)(q11q32)