Zinc fluxes and zinc transporter genes in chronic diseases

The group IIb metal zinc (Zn) is an essential dietary component that can be found in protein rich foods such as meat, seafood and legumes. Thousands of genes encoding Zn binding proteins were identified, especially after the completion of genome projects, an indication that a great number of biological processes are Zn dependent. Imbalance in Zn homeostasis was found to be associated with several chronic diseases such as asthma, diabetes and Alzheimer's disease. As it is now evident for most nutrients, body Zn status results from the interaction between diet and genotype. Zn ions cross biological membranes with the aid of specialized membrane proteins, belonging to the ZRT/IRT-related Proteins (ZIP) and zinc transporters (ZnT) families. The ZIPs are encoded by the Slc39A gene family and are responsible for uptake of the metal, ZnTs are encoded by the Slc30A genes and are involved in intracellular traffic and/or excretion. Both ZnTs and Zips exhibit unique tissue-specific expression, differential responsiveness to dietary Zn deficiency and excess, as well as to physiological stimuli via hormones and cytokines. Intracellular Zn concentration is buffered by metallothioneins (MTs), a class of cytosolic protein with high affinity for metals. Scattered information is available on the role of proteins responsible for regulating Zn fluxes in the onset and progression of chronic diseases. This paper reviews reports that link Zn transporter genes, their allelic variants and/or expression profiles in the context of specific diseases. Further investigation in this direction is very important, since Zn imbalance can result not only from insufficient dietary intake, but also from impaired activity of proteins that regulate Zn metabolism, thus contributing to multifactorial diseases.