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Association of tumor necrosis factor-? -308 G/A gene polymorphism with coronary artery diseases: An evidence-based study.

ABSTRACT: BACKGROUND:Coronary artery disease (CAD) is the leading cause of death worldwide and remains a major health problem, providing the rationale for identification of molecular markers for detection of individuals at high risk of developing CAD. Tumor necrosis factor-? (TNF-?) plays a crucial role in the pathogenesis of CAD. We have therefore explored the association of TNF-? 308 (G/A) gene polymorphism in 903 individuals with/without CAD. METHODS:TNF-? 308 gene polymorphism was analyzed in 903 subjects of whom 222 were healthy controls. Among the 681 patients who were investigated angiographically, 468 had ?50% stenosis and 213 patients had <50% stenosis. Biochemical profiles (eg, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, and CRP) were evaluated. Associations between TNF-? genotypes with biochemical and anthropometric characteristics were determined. RESULTS:The frequencies of TNF-?-AA or AG genotypes were significantly lower in patients classified as CAD patients with ? or <50% obstruction in at least one coronary artery, compared to the control group. We observed that CAD patients with ?50% stenosis and with AA genotype were associated with higher risk of CAD with OR of 3.56 (95%CI: 1.02-12.41; P=.046) using multivariate analysis. Moreover, we found that TNF-?-308-AA genotype was associated with blood pressure and CRP level in CAD patients, compared to the wild type-genotype. CONCLUSION:Our data showed an association of TNF-?-308G/A polymorphism with CAD patients with ?50% obstruction, supporting the need for further investigations on the role of TNF-?-308G/A polymorphism with hypertension.

SUBMITTER: Kazemi E

PROVIDER: S-EPMC6817255 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Association of tumor necrosis factor-α -308 G/A gene polymorphism with coronary artery diseases: An evidence-based study.

Kazemi Elaheh E Jamialahmadi Khadijeh K Avan Amir A Mirhafez Seyed Reza SR Mohiti Javad J Pirhoushiaran Maryam M Hosseini Nedasadat N Mohammadi Akram A Ferns Gordon A GA Pasdar Alireza A Ghayour-Mobarhan Majid M

Journal of clinical laboratory analysis 20170223 1

<h4>Background</h4>Coronary artery disease (CAD) is the leading cause of death worldwide and remains a major health problem, providing the rationale for identification of molecular markers for detection of individuals at high risk of developing CAD. Tumor necrosis factor-α (TNF-α) plays a crucial role in the pathogenesis of CAD. We have therefore explored the association of TNF-α 308 (G/A) gene polymorphism in 903 individuals with/without CAD.<h4>Methods</h4>TNF-α 308 gene polymorphism was analy ...[more]

PMID: 28233393

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Project description:Background and Objectives: Tumor necrosis factor alpha (TNF-α) is proatherogenic and associated with the risk of acute ischemic events, although the mechanisms that regulate TNF-α expression in stable coronary artery disease (SCAD) are not fully understood. We investigated whether metabolic, inflammatory, and epigenetic (microRNA (miRNA)) markers are associated with TNF-α expression in SCAD. Materials and Methods: Patients with SCAD were prospectively recruited and their metabolic and inflammatory profiles were assessed. TNF-α levels were assessed using an enzyme-linked immunosorbent assay. The relative expression of six circulating miRNAs associated with the regulation of inflammation and/or atherosclerosis was determined. Results: Of the 24 included patients with the mean age of 65 (9) years, 88% were male, and 54% were diabetic. The TNF-α levels were (median (interquartile range)) 1.0 (0.7-1.1) pg/mL. The percentage of glycosylated hemoglobin (r = 0.418, p = 0.042), serum triglyceride levels (r = 0.429, p = 0.037), and C-reactive protein levels (r = 0.407, p = 0.048) were positively correlated with TNF-α levels. Of the candidate miRNAs, miR-146a expression levels were negatively correlated with TNF-α levels (as indicated by r = 0.500, p = 0.035 for correlation between delta cycle threshold (ΔCt) miR-146a and TNF-α levels). In multivariate analysis, serum triglyceride levels and miR-146a expression levels were independently associated with TNF-α levels. miR-146 expression levels were not associated with metabolic or other inflammatory parameters and were negatively correlated with the number of coronary vessels with obstructive disease (as indicated by r = 0.556, p = 0.017 for correlation between ΔCt miR-146a and number of diseased vessels). Conclusions: miR-146a expression levels were negatively correlated with TNF-α levels in patients with SCAD, irrespective of other metabolic or inflammatory markers, and with the severity of coronary artery disease. The results add to the knowledge on the role of miR-146a in TNF-α-based inflammation in SCAD and support future research on the potential therapeutic use of miR-146a in such a clinical scenario.

Dataset Information

Association of tumor necrosis factor-? -308 G/A gene polymorphism with coronary artery diseases: An evidence-based study.

Publications

Association of tumor necrosis factor-α -308 G/A gene polymorphism with coronary artery diseases: An evidence-based study.

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