Elaheh Kazemi1,2, Khadijeh Jamialahmadi3,4, Amir Avan5, Seyed Reza Mirhafez6, Javad Mohiti1, Maryam Pirhoushiaran2, Nedasadat Hosseini2, Akram Mohammadi2, Gordon A Ferns7, Alireza Pasdar2,8, Majid Ghayour-Mobarhan5. 1. Department of Biochemistry, International Campus of Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 2. Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 4. Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 5. Metabolic syndrome Research center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 6. Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran. 7. Division of Medical Education, Brighton & Sussex Medical School, Brighton, Sussex, UK. 8. Division of Applied Medicine, Medical School, University of Aberdeen, Aberdeen, UK.
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-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. METHODS: TNF-α 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-α genotypes with biochemical and anthropometric characteristics were determined. RESULTS: The frequencies of TNF-α-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-α-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-α-308G/A polymorphism with CAD patients with ≥50% obstruction, supporting the need for further investigations on the role of TNF-α-308G/A polymorphism with hypertension.
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-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. METHODS: TNF-α 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-α genotypes with biochemical and anthropometric characteristics were determined. RESULTS: The frequencies of TNF-α-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-α-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-α-308G/A polymorphism with CAD patients with ≥50% obstruction, supporting the need for further investigations on the role of TNF-α-308G/A polymorphism with hypertension.
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