Association of tumor necrosis factor‐α ‐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‐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.

The association of interleukin-6 gene with obesity in patients with coronary artery disease

“…Control group consisted of 136 people, among them -63 men and 73 women aged from 45 up to 65 years without cardiovascular pathology and serious chronic illness [1]. 266 patients with CHF and EF lower than 40 % have been included in other research, no associations between TNF-α plasma concentration and TNF-α (308 A/G, 238 A/G, TNF beta Ncol and 3TACE) gene polymorphism have been observed [2].…”

Association of TNF-α (-308G/A) Gene Polymorphism with Circulating TNF-α Levels and Excessive Daytime Sleepiness in Adults with Coronary Artery Disease and Concomitant Obstructive Sleep Apnea

“…One explanation for the higher -308A allele frequency in the no-OSA group in our study might be the confounding effect of other comorbidities such as obesity, hypertension and diabetes mellitus and/or CAD per se, given that those individuals without OSA were not healthy controls. Similar to OSA, CAD is an inflammatory condition mediated by the activity of pro-inflammatory cytokines including TNF-α [ 37 ].…”

“…The role of TNF-α gene polymorphism in CAD pathogenesis has been extensively investigated with inconsistent results. Some researchers have reported that TNF-α -308G/A polymorphism is implicated in CAD development [ 37 , 38 ], whereas some others reported no evidence in this context [ 39 ]. It is suggested that the implication of the polymorphism in CAD pathogenesis differs between geographical ethnicities, and there was no significant association of TNF-α -308G/A polymorphism with the development of CAD according to a recent meta-analysis [ 26 ].…”

Protein Cytokines, Cytokine Gene Polymorphisms, and Potential Acute Coronary Syndrome Symptoms

“…Taken as a whole, our pilot gene associations were in the expected direction; that is, we observed increased risk of symptoms in the presence of TNF risk alleles. A number of studies found that, among cytokine SNPs, TNF rs1800629 and IL6 rs1800795 were significantly associated with CAD, and these SNPs were important risk factors for the development of ACS (Ansari et al, 2017;Babu et al, 2012;Kazemi et al, 2018).…”