Involvement of -308 TNF-alpha and 1267 Hsp70-2 polymorphisms and zinc status in the susceptibility of coronary artery disease (CAD) in old patients.
Coronary artery disease (CAD) is characterized by an inflammatory status and it represents the major cause of death in elderly. Zinc deficiency and inflammatory genes within major histocompatibility complex (MHC) region are implicated in ischaemic heart diseases. TNF-alpha is present in coronary artery plaques and may provoke plaque instability. Hsp70 plays instead a pro-atherogenic role, via proinflammatory cytokine production, in atherosclerotic lesions contributing to plaque rupture. Contradictory data report the association between -308 TNF-alpha polymorphism and CAD, while no investigations exist on Hsp70-2 gene in CAD. In the current study, we analysed -308 TNF-alpha and 1267 Hsp70-2 polymorphisms and zinc status in 190 healthy old controls and 216 old patients with carotid stenosis subdivided in two groups: the first one 105 patients with CAD (C group), and the second one 111 patients without cardiovascular events (D group). We found a lack of association between -308 TNF-alpha polymorphism and CAD. Conversely, 1267 Hsp70-2 polymorphism was associated with CAD. In particular, significant higher frequency of AB + BB genotypes (B + genotype) was observed in C patients than controls (71.4 vs.56.9%, P = 0.017, odds ratio = 1.898). However, when C patients were subdivided into four subgroups on the basis of presence/absence of 1267B Hsp70-2 and -308A TNF-alpha alleles, B + A + patients showed higher prothrombin activity as well as Hsp70-2, TNF-alpha, IL-6 gene expressions in carotid atheroma when compared to B - A - genotypes. The zinc status (plasma and Zn/Fe ratio in erythrocytes) is not affected by these polymorphisms. However, zinc deficiency is present in CAD condition. In conclusion, 1267 HSP70-2 polymorphism and zinc deficiency, rather than -308 TNF-alpha, are independently associated with CAD. B + A+ and B + A- carriers seem more predisposed to ischaemic events; conversely, B - A- genotype may be considered a protective marker against CAD.
Giacconi
Robertina
R
Immunolgy Ctr. (Section Nutrition, Immunity and Ageing), Res. Dept. INRCA, Via Birarelli 8, 60121, Ancona, Italy.
Cipriano
Catia
C
Muti
Elisa
E
Costarelli
Laura
L
Malavolta
Marco
M
Caruso
Calogero
C
Lio
Domenico
D
Mocchegiani
Eugenio
E
D000368:Aged; D000375:Aging / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D016893:Carotid Stenosis / Q000097:blood / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D007558:Italy; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D015032:Zinc / Q000097:blood* / Q000172:deficiency
D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015032:Zinc