title: Zinc deficiency and IL-6 -174G/C polymorphism in old people from different European countries: effect of zinc supplementation. ZINCAGE study.
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 < or = 10.5microM showed the worst immune response and psychological functions. Supplementation was carried out in C+ and C- carriers with stable low plasma zinc levels ( < or =10.5microM at baseline and at 1 year follow-up) and in C- carriers with unstable plasma zinc (< or =10.5microM at baseline and >10.5microM at 1 year follow-up). C+ carriers with plasma zinc >10.5microM were not supplemented because showing the best immune and psychological conditions. After 48+/-2 days of supplementation with 10mg/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.
authors.affiliation: Nutrigenomic and Immunosenescence Laboratory, Research Department, INRCA, Ancona, Italy. e.mocchegiani@inrca.it
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mocchegiani
authors.forename: Robertina
authors.initials: R
authors.lastname: Giacconi
authors.forename: Laura
authors.initials: L
authors.lastname: Costarelli
authors.forename: Elisa
authors.initials: E
authors.lastname: Muti
authors.forename: Catia
authors.initials: C
authors.lastname: Cipriano
authors.forename: Silvia
authors.initials: S
authors.lastname: Tesei
authors.forename: Sara
authors.initials: S
authors.lastname: Pierpaoli
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giuli
authors.forename: Roberta
authors.initials: R
authors.lastname: Papa
authors.forename: Fiorella
authors.initials: F
authors.lastname: Marcellini
authors.forename: Nazzarena
authors.initials: N
authors.lastname: Gasparini
authors.forename: Romeo
authors.initials: R
authors.lastname: Pierandrei
authors.forename: Francesco
authors.initials: F
authors.lastname: Piacenza
authors.forename: Ermina
authors.initials: E
authors.lastname: Mariani
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.forename: George
authors.initials: G
authors.lastname: Dedoussis
authors.forename: Stavroula
authors.initials: S
authors.lastname: Kanoni
authors.forename: Georges
authors.initials: G
authors.lastname: Herbein
authors.forename: Tamas
authors.initials: T
authors.lastname: Fulop
authors.forename: Lothar
authors.initials: L
authors.lastname: Rink
authors.forename: Jolanta
authors.initials: J
authors.lastname: Jajte
authors.forename: Marco
authors.initials: M
authors.lastname: Malavolta
mesh_terms: D000368:Aged; D003072:Cognition Disorders / Q000235:genetics; D019587:Dietary Supplements; D005260:Female; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D007477:Ions; D007963:Leukocytes, Mononuclear; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D014131:Trace Elements / Q000008:administration & dosage*; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency*
chemical_list: D015850:Interleukin-6; D007477:Ions; D014131:Trace Elements; D008668:Metallothionein; D015032:Zinc