647 A/C and +1245 MT1A polymorphisms in the susceptibility of diabetes mellitus and cardiovascular complications

• Published in: Molecular genetics and metabolism Vol. 94; no. 1; pp. 98 - 104
• Main Authors: Giacconi, R., Bonfigli, A.R., Testa, R., Sirolla, C., Cipriano, C., Marra, M., Muti, E., Malavolta, M., Costarelli, L., Piacenza, F., Tesei, S., Mocchegiani, E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2008
• Subjects: Aged; Cardiovascular diseases; Cardiovascular Diseases - complications; Cardiovascular Diseases - genetics; Diabetes Complications - genetics; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Elderly; Female; Flow Cytometry; Genetic Predisposition to Disease; Humans; Male; Metallothionein - genetics; Middle Aged; MT polymorphism; Polymorphism, Single Nucleotide; Type 2 diabetes; Zinc; Zinc - blood; Zinc - metabolism; Type 2 diabetes; MT polymorphism; Cardiovascular diseases; Elderly; Zinc
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2007.12.006

Diabetes mellitus is a chronic disease characterized by an overproduction of reactive oxygen species, which perturbs zinc metabolism and promotes the onset of cardiovascular disease (CVD) in diabetic patients.
Metallothioneins (MT) are cysteine-rich metal-binding proteins which, by means of their antioxidant and zinc-buffering properties, might prevent the development of diabetic cardiovascular complications.
A recent investigation shows that a polymorphism (+647 A/C) in the human MT-1A gene, affects the intracellular zinc ion release (iZnR) from the proteins and is associated with longevity in Italian population.
The aim of the present study is to assess the involvement of +647 A/C and +1245 A/G MT1A polymorphisms with the susceptibility to type 2 diabetes (DM2) and cardiovascular complications. The study included 694 old individuals: 242 old healthy controls, 217 DM2 patients without clinical evidence of CVD (DNC) and 235 diabetic patients with diagnosis of CVD (DCVD).
+647 A/C MT1A polymorphism, but not the second SNP, was associated with DM2. C allele carriers were more prevalent in DNC and DCVD patients than in control group (OR
=
1.37,
p
=
0.034; OR
=
1.54,
p
=
0.002, respectively). C+ carriers was associated with higher glycemia and glycosylated hemoglobin in DCVD patients, but not in DNC or control subjects. No differences in plasma zinc, but a modulation of MT levels and iZnR in PBMCs were observed in DCVD cohort when related to +647 A/C MT1A polymorphism. In summary, this work provides novel evidence on the association of the +647 A/C MT1A polymorphism with DM2. Moreover, C+ carriers in DCVD patients presented a worse glycemic control, a reduced iZnR and a higher MT levels, suggesting a possible role of MT in diabetic cardiovascular complications.