Association of MT1A haplotype with cardiovascular disease and antioxidant enzyme defense in elderly Greek population: comparison with an Italian cohort.
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.
Giacconi
Robertina
R
Nutrition and Aging, INRCA, Ancona, Italy. r.giacconi@inrca.it
Kanoni
Stavroula
S
Mecocci
Patrizia
P
Malavolta
Marco
M
Richter
Dimitris
D
Pierpaoli
Sara
S
Costarelli
Laura
L
Cipriano
Catia
C
Muti
Elisa
E
Mangialasche
Francesca
F
Piacenza
Francesco
F
Tesei
Silvia
S
Galeazzi
Roberta
R
Theodoraki
Eirini V
EV
Lattanzio
Fabrizia
F
Dedoussis
George
G
Mocchegiani
Eugenio
E
D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000235:genetics*; D016022:Case-Control Studies; D002374:Catalase / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D005979:Glutathione Peroxidase / Q000097:blood; D006115:Greece; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000097:blood
C530099:MT1A protein, human; D008668:Metallothionein; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase