title: Polymorphisms in MT1a gene coding region are associated with longevity in Italian Central female population.
abstract: Metallothioneins (MTs) play a pivotal role in zinc-related cell homeostasis because of their high affinity for zinc, which is in turn fundamental for immune response and antioxidant activity. MTs regulate zinc homeostasis by binding zinc and releasing zinc at the occurrence for immune response. The zinc release by MT is very limited in chronic inflammation and ageing. Some polymorphisms of MTs gene, in particular MT1a sub-isoform, may affect this release that is a problem still unresolved in ageing. The screening in the present paper of two polymorphisms in MT1a gene has revealed for the first time that the polymorphism corresponding to a A/C (Asp/Thr) transition at 647 nt position in the Mt1a coding region is the more involved in the longevity, at least in old women, rather than the other corresponding to A/G (Lys/Arg) transition at 1,245 nt position. Concomitantly, for the +647 MT1a polymorphism, old and very old female with Asp/Asp genotype (called C-carriers) display higher zinc release by MT (detected by Zinpyr-1 fluorescent probe in presence of NO donor), low MT levels and reduced IL-6 plasma concentrations, suggesting its involvement in longevity and in lower inflammatory status. This fact is confirmed by the analysis of haplotypes in which the allele Asp is more involved in longevity. Therefore the +647 MT1a polymorphism more affects MTs induction and zinc release, which are indispensable to undertake the inflammatory status under control and subsequently to reach healthy longevity.
authors.affiliation: Immunology Ctr. (Section: Nutrition and Immunosenescence), Res. Dept. INRCA, Via Birarelli 8, 60121, Ancona, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Cipriano
authors.forename: Marco
authors.initials: M
authors.lastname: Malavolta
authors.forename: Laura
authors.initials: L
authors.lastname: Costarelli
authors.forename: Robertina
authors.initials: R
authors.lastname: Giacconi
authors.forename: Elisa
authors.initials: E
authors.lastname: Muti
authors.forename: Nazzarena
authors.initials: N
authors.lastname: Gasparini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cardelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.forename: Erminia
authors.initials: E
authors.lastname: Mariani
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mocchegiani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D006834:Hydrazines; D015850:Interleukin-6 / Q000097:blood; D007558:Italy; D008136:Longevity / Q000235:genetics*; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D020030:Nitric Oxide Donors; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D013054:Spectrophotometry, Atomic; D015032:Zinc / Q000097:blood / Q000378:metabolism*
chemical_list: D005452:Fluoresceins; D005456:Fluorescent Dyes; D006834:Hydrazines; C508600:IL6 protein, human; D015850:Interleukin-6; D020030:Nitric Oxide Donors; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D008668:Metallothionein; D015032:Zinc; C501987:zinpyr-1