CD14 C (-260)T polymorphism, atherosclerosis, elderly: Role of cytokines and metallothioneins

Giacconi, Robertina; Caruso, Calogero; Lio, Domenico; Muti, Elisa; Cipriano, Catia; Costarelli, Laura; Saba, Vittorio; Gasparini, Nazzarena; Malavolta, Marco; Mocchegiani, Eugenio

doi:10.1016/j.ijcard.2006.08.035

Cited by 17 publications

(7 citation statements)

References 47 publications

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“…High MT levels during aging are correlated with low zinc availability and impaired inflammatory immune response, likely contributing to the development of age-related diseases, including atherosclerosis (16,15,26,32). Indeed, zinc deficiency has been suggested as a risk factor for atherosclerosis development (6,33), because the cation acts as a cofactor of antioxidant enzymes and protects from lipid peroxidation (34).…”

Section: Discussionmentioning

confidence: 99%

“…Low magnesium concentration has been linked to increased rate of cerebrovascular events (53), copper and zinc decrease in ulcerated plaques can promote atheroma destabilization (2) and, as for iron, an overload of this element leads to higher production of reactive oxygen species with subsequent atherosclerosis progression or cardiovascular diseases (12). Furthermore, high MT levels have been linked to atheroma, especially in the case of proinflammatory genotypes (26,32). The increased MT levels and reduced zinc availability that we found in PBMCs may also occur in atherosclerotic lesions, with consequent severe inflammation, oxidative stress, and ultimately plaque weakness.…”

Section: Discussionmentioning

confidence: 99%

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The +838 C/G MT2A Polymorphism, Metals, and the Inflammatory/Immune Response in Carotid Artery Stenosis in Elderly People

Giacconi

Muti

Malavolta

et al. 2007

Mol Med

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Carotid artery stenosis (CS) is a well-established risk factor for stroke. Increased proinflammatory chemokines, enhanced metallothionein (MT), and altered metal homeostasis may play roles in atherosclerosis progression and plaque destabilization. MT may sequester zinc during chronic inflammation, provoke zinc deficiency, and modulate NK cell cytotoxicity. A recent investigation of older patients with diabetes and atherosclerosis showed an association between the -209 A/G MT2A polymorphism, CS, and zinc status. In this study, we evaluated the relationship between two MT2A polymorphisms (-209 and + 838 locus), metal status, and inflammatory/immune response in older patients with CS only (the CS1 group) or with CS and previous cerebrovascular episodes (transient ischemic attack or stroke) (the CS2 group). A total of 506 individuals (188 CS1, 100 CS2, and 218 healthy controls) were studied. Atherosclerotic patients (CS1 and CS2) showed increased levels of MT, MCP-1, and RANTES, reduced NK cell cytotoxicity, and altered trace element concentrations (zinc, copper, magnesium, iron). The +838 C/G MT2A polymorphism was differently distributed in CS1 and CS2 patients, who displayed the GG genotype (C-) with significantly higher frequency than elderly controls. C-carriers showed increased MCP-1 and decreased NK cell cytotoxicity, CD56+ cells, and intracellular zinc availability along with decreased zinc, copper, and magnesium content in erythrocytes and increased iron in plasma. C-carriers also showed a major incidence of soft carotid plaques. In conclusion, the +838 C/G MT2A polymorphism seems to influence inflammatory markers, zinc availability, NK cell cytotoxicity, and trace element status, all of which may promote CS development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The +838 C/G MT2A Polymorphism, Metals, and the Inflammatory/Immune Response in Carotid Artery Stenosis in Elderly People

Giacconi

Muti

Malavolta

et al. 2007

Mol Med

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“…Contrarily, other studies have not corroborated these findings and showed a lack of association between C(-260)T CD14 promoter and susceptibility to atherosclerosis and risk of MI [65][66][67]. Finally, a recent study, performed in a central Italy elderly population with atherosclerotic carotid stenosis, showed an increased TT homozygote frequency of C-260T polymorphism, providing insight into the pathogenetic role of this polymorphism in atherosclerosis [68].…”

Section: Ccr5mentioning

confidence: 91%

Pharmacogenomics: A Tool to Prevent and Cure Coronary Heart Disease

Candore

Balistreri²,

Caruso³

et al. 2007

CPD

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Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). This is supported by epidemiological studies which have thoroughly investigated the association between CHD and gene polymorphisms of the inflammatory molecules. Moreover, efforts to find elective therapy have not been rewarding and, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. A critical search of published literature has suggested few inflammatory genes directly involved in the risk to develop CHD and MI. The selected genes are, the pro- and anti-inflammatory cytokines, Toll-like receptor 4 (TLR4), CD14, CCR5, cyclooxygenases (COXs) and lipoxygenases (LOXs). The associations between candidate gene polymorphisms and CHD/MI are difficult and complex as a consequence of pleiotropy, variations with age, selection due to the lethality of the disease, and interactions with other genes and environmental factors. However, current data indicate that screening for interleukin (IL)-6, IL-10, TLR4, CCR5, COX and LOX polymorphisms are likely to be a useful tool for CHD and MI risk assessment. What we believe is that dissecting out the influence of genetics polymorphism within the complex pathophysiology of CHD and MI will help to provide a more complete risk assessment and complement known classical cardiological risk factors. The detection of a risk profile will potentially allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug of lifestyle modification.

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“…Single nucleotide polymorphisms (SNPs) of immune functional factors appears to play important roles in cardiovascular disease [8] – [12] . Studies of the association study between ICAM-1 polymorphisms and cardiovascular disease focused on two SNPs in exons, including K469E and G241R [13] , [14] .…”

Section: Introductionmentioning

confidence: 99%

Association between the Polymorphisms in Intercellular Adhesion Molecule-1 and the Risk of Coronary Atherosclerosis: A Case-Controlled Study

Yang

Zhang

et al. 2014

PLoS ONE

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Intercellular adhesion molecule-1 (ICAM-1), an important immune adhesion molecule, is related to the atherosclerosis. We explored the association between the polymorphisms of the ICAM-1 gene and coronary atherosclerotic stenosis to determine whether any risk factors correlate with genetic polymorphisms in Chinese patients with coronary atherosclerosis. Using the SNaPshot assay, we examined six SNPs of rs5491, rs281428, rs281432, rs5496, rs5498 and rs281437 in 604 patients diagnosed with coronary atherosclerotic stenosis by angiography and in 468 controls. We found that AG genotype of rs5498 had higher frequency in the coronary atherosclerotic stenosis patients (41.56% to 34.19%, P = 0.017, OR = 1.368,95%CI 1.057–1.770) and that the haplotype Ars5491Crs281428Grs281432 had higher frequency in patients (13.8% to 12.1%, P = 0.048). When analyzing the clinical risk factors for coronary atherosclerosis, we found that the rs5498 locus was associated with the levels of apolipoprotein A (APOA) (P = 0.0002) and triglycerides (TG) (P = 0.002). Furthermore, the levels of triglycerides (TG) were also associated with rs281432 (P = 0.040). Additionally, the TT genotype of rs281437 was associated with a higher level of apolipoprotein A (APOA) (P = 0.039) and apolipoprotein B (APOB) (P = 0.003). Finally, among those with coronary atherosclerosis, we found no differences in the haplotype analysis of polymorphisms of the ICAM-1 gene from individuals with hypertension or those who smoked. According to our results, the ICAM-1 polymorphisms were associated with risk of coronary atherosclerotic stenosis in Chinese individuals.

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CD14 C (-260)T polymorphism, atherosclerosis, elderly: Role of cytokines and metallothioneins

Cited by 17 publications

References 47 publications

The +838 C/G MT2A Polymorphism, Metals, and the Inflammatory/Immune Response in Carotid Artery Stenosis in Elderly People

The +838 C/G MT2A Polymorphism, Metals, and the Inflammatory/Immune Response in Carotid Artery Stenosis in Elderly People

Pharmacogenomics: A Tool to Prevent and Cure Coronary Heart Disease

Association between the Polymorphisms in Intercellular Adhesion Molecule-1 and the Risk of Coronary Atherosclerosis: A Case-Controlled Study

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