Novel-209A/G MT2A polymorphism in old patients with type 2 diabetes and atherosclerosis: Relationship with inflammation (IL-6) and zinc

被引:74
作者
Giacconi, R
Cipriano, C
Muti, E
Costarelli, L
Maurizio, C
Saba, V
Gasparini, N
Malavolta, M
Mocchegiani, E
机构
[1] INRCA, Res Dept, Ctr Immunol, Sect Nutr Immun & Ageing, I-60121 Ancona, Italy
[2] INRCA, Dept Res, Genet & Mol Biol Ctr, Ancona, Italy
[3] INRCA Geriatr Hosp, Dept Surg Pathol, Ancona, Italy
关键词
atherosclerosis; elderly; inflammation; MT2A polymorphism; type; 2; diabetes; zinc;
D O I
10.1007/s10522-005-4907-y
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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.
引用
收藏
页码:407 / 413
页数:7
相关论文
共 28 条
[1]   Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: A short review [J].
Adeghate, E .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2004, 261 (1-2) :187-191
[2]   Regulation of metallothionein gene expression by oxidative stress and metal ions [J].
Andrews, GK .
BIOCHEMICAL PHARMACOLOGY, 2000, 59 (01) :95-104
[3]  
Barzilay Joshua, 2003, Treat Endocrinol, V2, P85, DOI 10.2165/00024677-200302020-00002
[4]   Is zinc deficiency a risk factor for atherosclerosis? [J].
Beattie, JH ;
Kwun, IS .
BRITISH JOURNAL OF NUTRITION, 2004, 91 (02) :177-181
[5]   Inflammatory bio-markers and cardiovascular risk prediction [J].
Blake, GJ ;
Ridker, PM .
JOURNAL OF INTERNAL MEDICINE, 2002, 252 (04) :283-294
[6]   Zinc, insulin and diabetes [J].
Chausmer, AB .
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION, 1998, 17 (02) :109-115
[7]   Inflammation: the link between insulin resistance, obesity and diabetes [J].
Dandona, P ;
Aljada, A ;
Bandyopadhyay, A .
TRENDS IN IMMUNOLOGY, 2004, 25 (01) :4-7
[8]   Zinc in relation to diabetes and oxidative disease [J].
DiSilvestro, RA .
JOURNAL OF NUTRITION, 2000, 130 (05) :1509S-1511S
[9]   Protective effects of antioxidant micronutrients (vitamin E, zinc and selenium) in type 2 diabetes mellitus [J].
Faure, P .
CLINICAL CHEMISTRY AND LABORATORY MEDICINE, 2003, 41 (08) :995-998
[10]   1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients [J].
Giacconi, R ;
Caruso, C ;
Lio, D ;
Muti, E ;
Cipriano, C ;
Saba, V ;
Boccoli, G ;
Gasparini, N ;
Malavolta, M ;
Mocchegiani, E .
MECHANISMS OF AGEING AND DEVELOPMENT, 2005, 126 (08) :866-873