Association of MT1A haplotype with cardiovascular disease and antioxidant enzyme defense in elderly Greek population: comparison with an Italian cohort |
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| Authors: | Robertina Giacconi Stavroula Kanoni Patrizia Mecocci Marco Malavolta Dimitris Richter Sara Pierpaoli Laura Costarelli Catia Cipriano Elisa Muti Francesca Mangialasche Francesco Piacenza Silvia Tesei Roberta Galeazzi Eirini V. Theodoraki Fabrizia Lattanzio George Dedoussis Eugenio Mocchegiani |
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| Affiliation: | 1. Nutrition and Aging, INRCA, Ancona, Italy;2. Department of Nutrition Science and Dietetics, Harokopio University, Athens, Greece;3. Euroclinics, Athens, Greece;4. Institute of Gerontology and Geriatrics, University of Perugia, Italy;5. Laboratory Analysis INRCA Hospital, Ancona, Italy;6. Scientific Direction, INRCA, Ancona, Italy;1. Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Miniami-ku, Sagamihara, Kanagawa 252-0373, Japan;2. Division of Hematology, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Miniami-ku, Sagamihara, Kanagawa 252-0373, Japan;1. Department of Biochemistry, Faculty of Medicine, Taif University, Al Taif, Saudi Arabia;2. Departments of Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt;3. Department of Surgery, Faculty of Medicine, Taif University, Al Taif, Saudi Arabia;4. General Organization for Teaching Hospitals and Institutes, Egypt;5. Department of Anatomy and Histology, Faculty of Medicine, Taif University, Al Taif, Saudi Arabia;6. Departments of Histology, Faculty of Medicine, Zagazig University, Zagazig, Egypt;1. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN;2. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN;3. Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN;4. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN;5. Departments of Geriatrics/Gerontology and Neurology, University of Mississippi Medical Center, Jackson, MS;6. Department of Epidemiology, University of Michigan Medical School, Ann Arbor, MI;1. Medical Research Service, Veterans Affairs Medical Center, Denver, CO, USA;2. Department of Psychiatry, University of Colorado, Anchutz Medical Campus, 12800 East 19th Avenue, Aurora, CO, USA;3. Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA |
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| Abstract: | Metallothioneins (MT), the antioxidant zinc-binding proteins, seem to mediate cardioprotection. It has been postulated that zinc homeostasis and MT function may be altered, as a consequence of oxidative stress, in cardiovascular disease (CVD), with a potential implication of MT genetic polymorphisms. The present study explores the role of +647A/C and +1245A/G MT1A polymorphisms on the susceptibility to CVD, zinc status and enzyme antioxidant activity, in the Greek and Italian populations. The country selection was based on the lower zinc status and the reduced zinc dietary intake in Greece than in Italy despite the similar Mediterranean dietary pattern. A total of 464 old, healthy control subjects and 369 old CVD patients more than 70 years of age were studied. Logistic regression model indicated that +1245 MT1A G+ genotype significantly increased the risk of CVD in Greece (34.4% vs. 23.2%; odds ratio=1.88, 95% confidence interval=1.14–3.08; P=.013) but not in Italy. Haplotype analysis showed an increment of CG haplotype frequency in CVD Greek patients (17.4% vs. 10.6%, P<.05). Differential country-related frequency distribution was also recorded. Applying a multivariate regression model, +647/+1245 MT1A haplotype was associated with a modulation of enzyme antioxidant activities in both countries. Decreased plasma zinc and reduced intracellular Zn release, as well as increased enzyme antioxidant activity, were more apparent in Greek healthy donors than in Italy. In conclusion, +1245 MT1A polymorphism and +647/+1245 MT1A haplotype are implicated in CVD in Greece but not in Italy, suggesting a role of gene–diet interaction in the disease predisposition. |
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