Pro-inflammatory genetic background and zinc status in old atherosclerotic subjects.
Inflammation and genetics are prominent mechanisms in the pathogenesis of atherosclerosis (AT) and its complications. In this review we discuss the possible impact on AT development of several genetic determinants involved in inflammation, oxidative stress and cytoprotection (IL-6, TNF-alpha, IL-10, CD14, TLR4, MT, HSP70). Genetic polymorphisms of these genes may affect a differential inflammatory response predisposing to AT. However, allelic polymorphisms of genes which increase the risk of AT frequently occur in the general population but, only adequate gene-environment-polymorphism interactions promote the onset of the disease. Zinc deficiency has been suggested as an environmental risk factor for AT. With advancing age, the incidence of zinc deficiency increases for several reasons. Among them, dietary intake, malabsorption and genetic background of inflammatory markers may be involved. A crucial contribution may also be played by increased oxidative stress which may lead to the appearance of dysfunctional proteins, including metallothioneins (MT) that are in turn involved in zinc homeostasis. The detection of candidate genes related to inflammation and promoting AT and their reciprocal influence/interaction with zinc status might allow earlier appropriate dietary interventions in genetically susceptible subjects.
Giacconi
Robertina
R
Immunolgy Center, Laboratory of Nutrigenomic and Immunosenenscence, Research Department, INRCA, Via Birarelli 8, 60121 Ancona, Italy. rogiacconi@libero.it
Caruso
Calogero
C
Malavolta
Marco
M
Lio
Domenico
D
Balistreri
Carmela R
CR
Scola
Letizia
L
Candore
Giuseppina
G
Muti
Elisa
E
Mocchegiani
Eugenio
E
D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008668:Metallothionein / Q000502:physiology; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D015032:Zinc / Q000172:deficiency* / Q000502:physiology
D008668:Metallothionein; D015032:Zinc