title: Effect of ZIP2 Gln/Arg/Leu (rs2234632) polymorphism on zinc homeostasis and inflammatory response following zinc supplementation.
abstract: Zinc dyshomeostasis may lead to an augmented production of proinflammatory cytokines promoting chronic inflammation and increasing the susceptibility to age-related diseases. Several studies suggest that the zinc transporter protein ZIP2 may play a relevant role in the immune system especially during zinc deficiency, while a polymorphism on the coding region of ZIP2 gene (Gln/Arg/Leu) has been associated with severe carotid artery disease. The aim of this study is to investigate the role of ZIP2 SNP on zinc and inflammatory status in 1090 elderly healthy free-living subjects enrolled in the ZincAge project and to assess the effect of zinc supplementation on zinc status, inflammatory mediators, and zinc transporter expression depending on ZIP2 genotype. ZIP2 Leu- (Arg43Arg) carriers showed enhanced IL-6, TNF-α, and RANTES plasma levels associated with decreased free cytosolic zinc in PBMCs and an upregulation of zinc transporters ZIP2, ZIP8, and Znt1. Moreover, Leu- subjects displayed significant decrement of inflammatory mediators such as MCP-1, TNF-α, and RANTES following zinc supplementation. In summary, this investigation provides new evidence on the effect of ZIP2 Gln/Arg/Leu polymorphism on proinflammatory mediators and zinc homeostasis in elderly population with a more pronounced anti-inflammatory effect of zinc supplementation in subjects carrying ZIP2 Leu- (Arg43Arg) genotype. These novel findings could be useful in identifying elderly subjects who may benefit of zinc intervention to decrease the inflammatory status and to prevent or delay the development of age-related diseases.
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: Robertina
authors.initials: R
authors.lastname: Giacconi
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Costarelli
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Malavolta
authors.affiliation: Advanced Technology Center for Aging Research, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cardelli
authors.affiliation: Clinical Laboratory and Molecular Diagnostics, INRCA-IRCCS, Ancona, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Galeazzi
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piacenza
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: Nazzarena
authors.initials: N
authors.lastname: Gasparini
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Basso
authors.affiliation: Department of Medical and Surgical Sciences, Laboratory of Immunereumatology and Tissue Regeneration/RAMSES, Rizzoli Orthopedic Institute, Bologna, University of Bologna, Italy.
authors.forename: Erminia
authors.initials: E
authors.lastname: Mariani
authors.affiliation: Department of Medicine Faculty of Medicine, Research Center on Aging, University of Sherbrooke, Canada.
authors.forename: Tamas
authors.initials: T
authors.lastname: Fulop
authors.affiliation: Institute of Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Rink
authors.affiliation: Department of Dietetics and Nutritional Science, Harokopio University of Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dedoussis
authors.affiliation: Department Pathogens and Inflammation EA 4266, Université Bourgogne Franche-Comté, CHRU Besançon, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Herbein
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Medical University, Lodz, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Jajte
authors.affiliation: Advanced Technology Center for Aging Research, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Provinciali
authors.affiliation: Clinical Laboratory and Molecular Diagnostics, INRCA-IRCCS, Ancona, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Busco
authors.affiliation: Translational Research Ctr. of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mocchegiani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D018946:Chemokine CCL5 / Q000097:blood; D019587:Dietary Supplements; D005260:Female; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D007107:Immune System / Q000378:metabolism; D007249:Inflammation / Q000097:blood* / Q000178:diet therapy / Q000235:genetics / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015032:Zinc / Q000097:blood* / Q000172:deficiency / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D027682:Cation Transport Proteins; D018946:Chemokine CCL5; D015850:Interleukin-6; C498424:SLC39A2 protein, human; D014409:Tumor Necrosis Factor-alpha; D015032:Zinc
keywords: ZIP2 Gln/Arg/Leu polymorphism; aging; inflammation; zinc homeostasis; zinc supplementation