Please cite this article in press as: C. Devirgiliis et al., Zinc fluxes and zinc transporter genes in chronic diseases, Mutat. Res.: Fundam. Mol. Mech. Mutagen. (2007), doi:10.1016/j.mrfmmm.2007.01.013 ARTICLE IN PRESS +Model MUT-10406; No. of Pages 10 Mutation Research xxx (2007) xxx–xxx Zinc fluxes and zinc transporter genes in chronic diseases Chiara Devirgiliis a , Peter D. Zalewski b , Giuditta Perozzi a , Chiara Murgia a,∗ a INRAN, National Research Institute on Food and Nutrition, Via Ardeatina 546 00178, Roma, Italy b Department of Medicine, University of Adelaide, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia Received 24 October 2006; received in revised form 16 January 2007; accepted 24 January 2007 Abstract 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. © 2007 Elsevier B.V. All rights reserved. Keywords: Zinc; Zinc transporters; Nutrigenomics; Chronic diseases 1. Zinc homeostasis Zinc (Zn) is an essential micronutrient that plays fundamental housekeeping roles in physiology, cellu- lar metabolism and gene expression. Zn is required as a catalytic cofactor of more than 300 enzymes and it stabilizes the structure of thousands of protein domains. Recently reported results of a global search within the ∗ Corresponding author. Tel.: +39 0651494457; fax: +39 0651494550. E-mail address: murgia@inran.it (C. Murgia). human genome database with a bioinformatics approach estimated that about 10% of the human proteome con- sists of potential Zn-binding proteins [1]. Therefore, a great number of biological processes are Zn dependent, and an imbalance of Zn homeostasis has complex impli- cations in a number of organs and can contribute to the onset of chronic pathologies [2,3]. The Recommended Daily Allowance (RDA) for Zn is 12–15 mg/day, in bal- anced diets this amount is obtained by eating meat and other sources of animal proteins. These foods have a high Zn content and the metal is bound to ligands, which facil- itate its absorption. Other sources of Zn are sea-foods, dairy products, cereals and nuts [4]. Most vegetables are 0027-5107/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.mrfmmm.2007.01.013