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

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.

• Authors: Robertina Giacconi, Elisa Muti, Marco Malavolta, Catia Cipriano, Laura Costarelli, Gianni Bernardini, Nazzarena Gasparini, Erminia Mariani, Vittorio Saba, Gianfranco Boccoli, Eugenio Mocchegiani
• Journal: Molecular medicine (Cambridge, Mass.) (Mol Med) 2007 Jul-Aug Vol. 13 Issue 7-8 Pg. 388-95 ISSN: 1076-1551 [Print] England
• PMID: 17622311 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL2 protein, human
• Chemokine CCL2
• Chemokine CCL5
• Chemokines
• MT2A protein, human
• Metals
• Metallothionein

Topics

• Aged
• Aged, 80 and over
• Carotid Stenosis (genetics, immunology)
• Chemokine CCL2 (metabolism)
• Chemokine CCL5 (metabolism)
• Chemokines (metabolism)
• Cytotoxicity, Immunologic (genetics)
• Female
• Gene Frequency
• Humans
• Inflammation (genetics)
• Killer Cells, Natural (immunology)
• Male
• Metallothionein (genetics)
• Metals (blood)
• Polymorphism, Genetic