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Zinc deficiency and IL-6 -174G/C polymorphism in old people from different European countries: effect of zinc supplementation. ZINCAGE study |
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| Authors: | Mocchegiani Eugenio Giacconi Robertina Costarelli Laura Muti Elisa Cipriano Catia Tesei Silvia Pierpaoli Sara Giuli Cinzia Papa Roberta Marcellini Fiorella Gasparini Nazzarena Pierandrei Romeo Piacenza Francesco Mariani Ermina Monti Daniela Dedoussis George Kanoni Stavroula Herbein Georges Fulop Tamas Rink Lothar Jajte Jolanta Malavolta Marco |
| Affiliation: | aNutrigenomic and Immunosenescence Laboratory, Research Department, INRCA, Ancona, Italy bGerontological and Psychological Center, Research Department, INRCA, Ancona, Italy cLaboratory of Immunology and Genetics, Istituto di Ricerca Codivilla Putti, IOR, Bologna, Department of Internal Medicine and Gastroenterology, University of Bologna, Italy dDepartment of Internal Medicine and Gastroenterology, University of Bologna, Italy eExperimental Pathology and Oncology, University of Florence, Florence, Italy fDepartment of Nutrition Science and Dietetics, Harokopio University of Athens, Greece gDepartment of Virology, Franche-Comte University, Besancon, France hResearch Center on Aging, Immunology Program, Geriatric Division, University of Sherbrooke, Canada iInstitute of Immunology, RWTH-Aachen University Hospital, Aachen, Germany jDepartment of Toxicology, Faculty of Pharmacy, Medical University, Lodz, Poland |
| Abstract: | IL-6 SNP at position −174 is associated with age-related diseases characterized by an impaired Zn status. This polymorphism seems also relevant in regulating the expression of proteins, such as Metallothioneins (MT), involved in the modulation of Zn homeostasis. Since high IL-6 levels in elderly induce hypozinchemia, the IL-6−174 SNP may be useful to identify old subjects who are at risk for Zn deficiency. The objectives of this study are: (1) to choose old subjects who effectively need Zn supplementation and (2) to study the effect of Zn supplementation on Zn, immune and psychological status in genetically selected subjects. For this purpose, a baseline study comprising 895 healthy old subjects recruited in Central-Northern and Southern European Countries was carried out by evaluating their dietary intake, psychological and immune parameters as well as their Zn status. A Zn supplementation trial was performed in 110 old subjects selected on the basis of their plasma Zn levels and IL-6 SNP. After correcting for age and Zn intake, C− carriers displayed higher MT and lower levels of several parameters related to zinc status (plasma Zn, erythrocyte Zn and NO-induced release of Zn in PBMC) than C+ carriers. Better NK cell cytotoxicity and psychological functions (PSS, MMSE) were also found in C+ than C− carriers strictly related to the zinc status. However, independently by the polymorphism, all subjects with plasma zinc 10.5 μM showed the worst immune response and psychological functions. Supplementation was carried out in C+ and C− carriers with stable low plasma zinc levels (10.5 μM at baseline and at 1 year follow-up) and in C− carriers with unstable plasma zinc (10.5 μM at baseline and >10.5 μM at 1 year follow-up). C+ carriers with plasma zinc >10.5 μM were not supplemented because showing the best immune and psychological conditions. After 48 ± 2 days of supplementation with 10 mg/day of Zn-aspartate, the NO-induced release of Zn, erythrocyte Zn and NK cell cytotoxicity increased in all groups selected for supplementation, including C− with unstable plasma zinc. In conclusion, the sole assessment of plasma Zn level is not reliable to exclude C− carriers from Zn supplementation. A possible explanation for the conflicting data on the identification of IL-6−174G as a “risk allele” based on different dietary intake in the studied population is also suggested. |
| Keywords: | IL-6 polymorphisms Zinc status Metallothioneins Genetic screening Ageing |
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