The +838 C/G MT2A polymorphism, metals, and the inflammatory/immune response in carotid artery stenosis in elderly people

Robertina Giacconi, Elisa Muti, Marco Malavolta, Catia Cipriano, Laura Costarelli, Gianni Bernardini, Nazzarena Gasparini, Erminia Mariani, Vittorio Saba, Gianfranco Boccoli, Eugenio Mocchegiani

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Abstract

Carotid artery stenosis (CS) is a well-established risk factor for stroke. Increased proinflammatory chemokines, enhanced metallothionein (MT), and altered metal homeostasis may play roles in atherosclerosis progression and plaque destabilization. MT may sequester zinc during chronic inflammation, provoke zinc deficiency, and modulate NK cell cytotoxicity. A recent investigation of older patients with diabetes and atherosclerosis showed an association between the -209 A/G MT2A polymorphism, CS, and zinc status. In this study, we evaluated the relationship between two MT2A polymorphisms (-209 and + 838 locus), metal status, and inflammatory/immune response in older patients with CS only (the CS1 group) or with CS and previous cerebrovascular episodes (transient ischemic attack or stroke) (the CS2 group). A total of 506 individuals (188 CS1, 100 CS2, and 218 healthy controls) were studied. Atherosclerotic patients (CS1 and CS2) showed increased levels of MT, MCP-1, and RANTES, reduced NK cell cytotoxicity, and altered trace element concentrations (zinc, copper, magnesium, iron). The +838 C/G MT2A polymorphism was differently distributed in CS1 and CS2 patients, who displayed the GG genotype (C-) with significantly higher frequency than elderly controls. C- carriers showed increased MCP-1 and decreased NK cell cytotoxicity, CD56+ cells, and intracellular zinc availability along with decreased zinc, copper, and magnesium content in erythrocytes and increased iron in plasma. C- carriers also showed a major incidence of soft carotid plaques. In conclusion, the +838 C/G MT2A polymorphism seems to influence inflammatory markers, zinc availability, NK cell cytotoxicity, and trace element status, all of which may promote CS development.

Original languageEnglish
Pages (from-to)388-395
Number of pages8
JournalMolecular medicine (Cambridge, Mass.)
Volume13
Issue number7-8
DOIs
Publication statusPublished - Jul 2007

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Carotid Stenosis
Zinc
Metals
Natural Killer Cells
Metallothionein
Trace Elements
Magnesium
Copper
Atherosclerosis
Iron
Stroke
Chemokine CCL5
Transient Ischemic Attack
Chemokines
Homeostasis
Erythrocytes
Genotype
Inflammation
Incidence

ASJC Scopus subject areas

  • Genetics

Cite this

The +838 C/G MT2A polymorphism, metals, and the inflammatory/immune response in carotid artery stenosis in elderly people. / Giacconi, Robertina; Muti, Elisa; Malavolta, Marco; Cipriano, Catia; Costarelli, Laura; Bernardini, Gianni; Gasparini, Nazzarena; Mariani, Erminia; Saba, Vittorio; Boccoli, Gianfranco; Mocchegiani, Eugenio.

In: Molecular medicine (Cambridge, Mass.), Vol. 13, No. 7-8, 07.2007, p. 388-395.

Research output: Contribution to journalArticle

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AU - Bernardini, Gianni

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