The objective of this study is to investigate the link between TNF-alpha (rs1800629) − 308 G/A genetic polymorphism and the risk or susceptibility to angina pectoris in its two forms in the Iraqi population, based on the supposition the IHD that include angina pectoris is a chronic inflammation condition. In this manner, the results suggest that the (rs1800629) − 308 A allelic variant was accompanied by changes TNF-alpha production and an increase in risk of angina pectoris in the Iraqi population. Several variations were identified in the promoter region of the human TNF gene, with the potential to establish structural changes inside regulatory regions, potentially disrupting the performance and management of TNF-alpha production or expression [8]. On the basis of the results of this study, it was revealed as the significant increase level of the TNF-alpha in the stable and unstable angina groups as compared with control. However, TNF-alpha is considered a pleiotropic cytokine that effects on the many activities of cellular system. Its effects are on the lipid metabolism, coagulation endothelial function, and insulin resistance [9].
Chronic inflammatory process is marked by elevated circulation levels of pro-inflammatory cytokines, adhesion molecules, and cytokine-responsive acute-phase proteins. Many of these inflammatory plasma indicators have been identified to predict future cardiovascular risk in patients with acute coronary syndrome. TNF-alpha levels in the blood have been linked to atherosclerosis of coronary artery risk factors such as dyslipidemia, overweight, and inflammation [10]. In a sample of stable and unstable coronary patients, TNF-alpha was significantly related to the severity of coronary disease. This connection could be an indication of chronic inflammatory load and a risk factor for severe coronary disease [11]. In this context, it should be noted that the (rs1800629) SNP has upregulate and elevate or modify the level of TNF-alpha protein. Therefore, the expression of cytokine was elevated by the existence of the − 308 A allele variant [9]. Consequently, [12] has clarified that the TNF-alpha transcription is increased by six- to eightfold when the single-nucleotide polymorphism − 308 G/A is present in the promoter region. Furthermore, polymorphisms that flank TNF genes have been shown to be meaningful biomarkers of TNF-alpha production and to influence transcription factor binding.
Further suggestion by [13] revealed that the TNF-alpha was a major contributor into types 1 and 2 diabetes predispositions in Iranian and Saudi patients, correspondingly. Furthermore, diabetes patients had three- to fourfold upregulate levels of circulating TNF-alpha than healthy controls. In a prior study on Egyptian patients, TNF-alpha was found to be strongly linked with cardiovascular risk factor such as TC, LDL-C, FBG, HbA1c, and creatinine [14]. According to [4], TNF-alpha enhances the inflammatory reaction and contributing to the clinical difficulties associated with cardiovascular disorder and autoimmune disease, both of which are closely linked to cardiovascular comorbidity. Hence, prior study has shown that the TNF-alpha is a significant cytokine involved in the advancement of different atherosclerotic conditions [15]. In this study, data analysis suggested five models of inheritance that differed significantly between all patients and control (P ≤ 0.05) with OR > 1. Thereby, the results sustained with [16] demonstrating that the individuals with the AA genotype or who held the A allele of the − 308 G/A polymorphism were more probably to have IHD. Taken together, these results indicate that TNF-alpha − 308 G/A polymorphism may have a significant impact on susceptibility to developing angina pectoris.
Genotypes and allele frequencies of TNF-alpha gene polymorphism showed a different genetic distribution between the studied groups. Both groups of patients with angina pectoris have significant differences of genotypes and G/A allele in comparison with control. These results can give information of the susceptibility for angina pectoris in the Iraqi patients by investigating the role of risk or protective alleles of (rs1800629) -308G/A at the promoter region of TNF-alpha gene. However, the possibility of attributable or etiological allele which has OR more than 1 exhibited risk factor in patients who is bearing the AA and/ or GA proportions and A allele. The results demonstrated that in the existence of the AA genotype, the concentration of TNF-alpha remained considerably higher in the examined groups, particularly in patients with unstable angina (106 ± 15.7). These observations imply that TNF-alpha may exhibit a role in the pathogenicity of angina pectoris among participants, which is genetically determined. Moreover, the (rs1800629) − 308 G/A has been the most studied variant of TNF-alpha, because numerous studies have found that the individual with the A allele possesses elevated rates of TNF-alpha in serum, significantly affecting the risk of developing CAD [17, 18]. Many case–control studies have been carried out to investigate the correlation between TNF-alpha -308 G/A polymorphism and cardiovascular disease, but the results have been equivocal. In 2007, a meta-analysis found no link between the G-308A polymorphism and CAD in groups primarily of European ancestry [19]. The study by [6] demonstrated that that there is no association between A allele of − 308 polymorphism of TNF-alpha gene and CAD in the Chinese population. Nevertheless, other meta-analysis published in 2011 found that the A allele of TNF-alpha gene imparted a 1.5-fold greater risk of developing CAD in Caucasians (AG + AA vs. GG, OR = 1.50; 95% CI: 1.23–1.77) [20]. To offer a more consistent and accurate evaluation of the link between the TNF-alpha − 308 G/A polymorphism and CAD risk, a meta-analysis of 36 datasets with 12,567 cases and 13,216 controls was performed. In this meta-analysis, high-quality research discovered a substantial link between the − 308 G/A polymorphism and CAD susceptibility in the general population [21]. TNF-alpha promoter genetic variations have been linked to TNF-alpha serum concentrations, which have been linked to first-time coronary heart disease and are a biomarker for repetitive cardiovascular events following a previous myocardial infarction [22]. Interestingly, the rs1800629 polymorphism, which might boost TNF gene transcriptional activity, associated with increased TNF-plasma levels in ischemic stroke etiology, and this result was confirmed by genetic association data analysis [23].