MT gene expression is induced by pro-inflammatory cytokines during stress and inflammation. The interrelationships among inflammatory cytokines, stress, MT expression level and zinc ion bioavailability are crucial in order to achieve healthy longevity (Mocchegiani and Malavolta, 2008). The analysis of some polymorphisms in MT genes confirms this assumption. The studies performed so far regarding the relation between several MT polymorphisms and aging and age related disease have been usually performed in Italy population by the same researchers group. Recent findings have showed that MT1A +647 A/C coding region polymorphism affects the inflammatory status, and this polymorphism is associated with longevity in Italian population (Cipriano et al., 2006). Also, MT1A +647 C+ carriers displayed higher IL-6 levels and they were more likely to develop type 2 diabetes and cardiovascular complications. However, in the same study, as concerning +1245 A/G MT1A polymorphism, no differences in genotypic and allelic distribution were found among healthy old control groups (Giacconi et al., 2008). In other polymorphism at the untranslated region of MT2A (+838 C/G), it is observed that elderly subjects carrying C(cid:2) allele had more risk to develop carotid artery stenosis (Giacconi et al., 2007). Giacconi

et al. (2008) reported a significant relationship between MT2A (cid:2)209 A/G promoter region polymorphism, diabetes type II and atherosclerosis disease. Moreover, they found out that G(cid:2) carriers display higher circulating IL-6 levels compared to G+. Another polymorphism regarding MT2A is (cid:2)5 A/G SNP, and this polymor- phism is located at the core promoter region of MT2A gene where the gene transcription initializes. There have been only a few studies on MT2A (cid:2)5 A/G SNP in the literature and a significant association has been found between this polymorphism and Cd levels in autopsy renal tissues (Kayaalti et al., 2010) whereas no

Z. Kayaaltı et al./Archives of Giacconi, R., Cipriano, C., Muti, E., Costarelli, L., Maurizio, C., Saba, V., Gasparini, N., Malavolta, M., Mocchegiani, E.,

Novel (cid:

)

A/G MT

A polymorphism in oldpatientswithtype

diabetesandatherosclerosis: relationshipwithinflam- mation (IL-

) and zinc. Biogerontology

,

–

Giacconi, R., Muti, E., Malavolta, M., Cipriano, C., Costarelli, L., Bernardini, G., Gasparini, N., Mariani, E., Saba, V., Boccoli, G., Mocchegiani, E.,

The +

C/G MT

A polymorphism, metals, and the inflammatory/immune re- sponse in carotid artery stenosis in elderly people. Mol. Med.

,

–

Giacconi, R., Bonfigli, A.R., Testa, R., Sirolla, C., Cipriano, C., Marra, M., Muti, E., Malavolta, M., Costarelli, L., Piacenza, F., Tesei, S., Mocchegiani, E.,

The +

A/C and +

MT

A polymorphisms in the susceptibility of diabetes mellitus and cardiovascular complications. Mol. Genet. Metab.

,

–

Haddy, N., Sass, C., Maumus, S., Marie, B., Droesch, S., Siest, G., Lambert, D., Visvikis, S.,

Biologicalvariations,geneticpolymorphismsandfamilialresemblance o

NF-alphaan

L-

concentrations:STANISLAScohort.Eur.J.Hum.Genet.

,

–

Hayashi,Y.,Hashizume,T.,Wakida,K.,Satoh,M.,Uchida,Y.,Watabe,K.,Matsuyama, Z., Kimura, A., Inuzuka, T., Hozumi, I.,

Association between metallothio- nein genes polymorphisms and sporadic amyotrophic lateral sclerosis in a Japanese population. Amyotroph. Lateral Scler.

,

–

Hjelmborg, B.J., Iachine, I., Skytthe, A., Vaupel, J.W., M

ue, M., Koskenvuo, M., Kaprio, J., Pedersen, N.L., Christensen, K.,

Genetic influence on human lifespan and longevity. Hum. Genet.

,

–

Hurme, M., Paavilainen, P.M., Pertovaara, M., Jylha¨, M., Karhunen, P.J., Hervonen, A., Lehtima¨ki, T.,

I

levels are predictors of mortality in Finnish nonagen- arians. Mech. Ageing Dev.

,

–

Jerrard-Dunne, P., Sitzer, M., Risley, P., Steckel, D.A., Buehler, A., von Kegler, S., Markus, H.S.,

Carotid Atherosclerosis Progression Study Interleukin-

promoter polymorphism modulates the effects of heavy alcohol consumption on early carotid artery atherosclerosis: the Carotid Atherosclerosis Progression Study (CAPS). Stroke

,

–

Jylha¨, M., Paavilainen, P., Lehtima¨ki, T., Goebeler, S., Karhunen, P.J., Hervonen, A., Hurme, M.,

Interleukin-

receptor antagonist, interleukin-

, and C-reac- tiveproteinaspredictorsofmortalityinnonagenarians:thevitality

+study.J. Gerontol. A: Biol. Sci. Med. Sci.

,

–

Kayaalti, Z., So¨ylemezog˘lu, T.,

The polymorphism of core promoter region on metallothionein

A-metalbindingproteini

urkishpopulation.Mol.Biol.Rep.

,

–

Kayaalti, Z., Mergen, G., So¨ylemezog˘lu, T.,

Effect of metallothionein core promoterregion polymorphismon cadmium, zinc and copper levels inautopsy kidney tissues from a Turkish population. Toxicol. Appl. Pharmacol.

,

–

Kita, K., Miura, N., Yoshida, M., Yamazaki, K., Ohkubo, T., Imai, Y., Naganuma, A.,

Potential effect on cellular response to cadmium of a single-nucleotide A ! G polymorphism in the promoter of the human gene for metallothionein IIA. Hum. Genet.

,

–

Kwon, C.S., Kountouri, A.M., Mayer, C., Gordon, M.J., Kwun, I.S., Beattie, J.H.,

Mononuclear cell metallothionein

NA levels in human subjects with poor zinc nutrition. Br. J. Nutr.

,

–

Mazzatti,D.J.,Malavolta,M.,White,A.J.,Costarelli,L.,Giacconi,R.,Muti,E.,Cipriano, C., Powell, J.R., Mocchegiani, E.,

Effects of interleukin-

(cid:

)

C/G and metallothionein

A +

A/C single-nucleotide polymorphisms on zinc-regu- lated gene expression in ageing. Exp. Gerontol.

,

–

Miles, A.T., Hawksworth, G.M., Beattie, J.H., Rodilla, V.,

Induction, regulation, degradation, and biological significance of mammalian metallothioneins. Crit. Rev. Biochem. Mol. Biol.

,

–

Mocchegiani, E., Malavolta, M.,

Zinc-gene interaction related to inflammato- ry/immune response in ageing. Genes Nutr.

,

–

Mocchegiani, E., Giacconi, R., Muti, E., Rogo, C., Bracci, M., Muzzioli, M., Cipriano, C., Malavolta,M.,