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.