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Novel -209A/G MT2A Polymorphism in Old Patients with Type 2 Diabetes and Atherosclerosis: Relationship with Inflammation (IL-6) and Zinc

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Abstract

Vascular complications, including ischaemic cardiomyopathy, are the major causes of death in old diabetic patients. Chronic inflammation due to high IL-6 production occurs in type 2 diabetes (NIDDM) and atherosclerosis. High levels of IL-6 are associated with hyperglycaemia, dyslipidemia and provoke insulin resistance. In ageing and inflammation, IL-6 affects Metallothionein (MT) homeostasis, which in turn is involved in zinc turnover. Zinc deficiency is an usual event in ageing, inflammation, type 2 diabetes and atherosclerosis. No genetic study exists on MT polymorphisms in NIDDM-atherosclerotic patients. The aim of the present study is to screen a single nucleotide polymorphism in the promoter region of the MT2A gene in relation to inflammation (IL-6) and plasma zinc in NIDDM-atherosclerotic patients. The -209 A/G MT2A polymorphism is associated with chronic inflammation (higher plasma levels of IL-6), hyperglycaemia, enhanced HbA1c and more marked zinc deficiency in AA than AG genotype carrying patients. Analysing patients and controls subdivided in AA and AG genotypes, significant interactions existed between disease status and genotypes for glucose and zinc. AA patients are more at risk of developing NIDDM in association with atherosclerosis (p = 0.0015 odds ratio = 2.617) and its complications, such as ischaemic cardiomyopathy (p = 0.0050 odds ratio = 12.6). In conclusion, high levels of IL-6 unmask the phenotypes (higher insulin resistance and zinc deficiency) in relation to the genotypes with subsequent risk of developing ischaemic cardiomyopathy in NIDDM-atherosclerotic patients carrying AA genotype. Hence, the novel -209A/G MT2A polymorphism may be a further useful tool for the prevention, diagnosis and therapy of these combined pathologies in the elderly.

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Abbreviations

NIDDM:

Non Insulin dependent Diabetes Mellitus (Type 2 diabetes)

MT:

Metallothionein

CHD:

Coronary Heart Disease

MI:

myocardial infarction

SNP:

single-nucleotide polymorphism

IL-6:

interleukin-6

HDL:

High density Lipoprotein

LDL:

Low density lipoprotein

BMI:

Body Mass Index

ECG:

Electro Cardio-Gram

HbA1c:

Glycosylated haemoglobin

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Authors and Affiliations

  1. Immunology Center (Section Nutrition, Immunity and Ageing), Res. Dept, INRCA, Via Birarelli 8, 60121, Ancona, Italy

    Robertina Giacconi, Catia Cipriano, Elisa Muti, Laura Costarelli, Nazzarena Gasparini, Marco Malavolta & Eugenio Mocchegiani

  2. Genetic and Molecular Biology Center, Res. Dept, INRCA, Ancona, Italy

    Cardelli Maurizio

  3. Department of Surgical Pathology, INRCA Geriatric Hospital, Ancona, Italy

    Vittorio Saba

Authors
  1. Robertina Giacconi
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  2. Catia Cipriano
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  3. Elisa Muti
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  4. Laura Costarelli
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  5. Cardelli Maurizio
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  6. Vittorio Saba
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  7. Nazzarena Gasparini
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  8. Marco Malavolta
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  9. Eugenio Mocchegiani
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Corresponding author

Correspondence to Eugenio Mocchegiani.

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Giacconi, R., Cipriano, C., Muti, E. et al. Novel -209A/G MT2A Polymorphism in Old Patients with Type 2 Diabetes and Atherosclerosis: Relationship with Inflammation (IL-6) and Zinc. Biogerontology 6, 407–413 (2005). https://doi.org/10.1007/s10522-005-4907-y

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  • DOI: https://doi.org/10.1007/s10522-005-4907-y

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