Atherosclerosis is an inflammatory disease. The ath­erosclerotic plaque shows many changes consistent with a chronic inflammatory process [1]. The pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) is present in atheromatous plaque macrophages, smooth muscle cells and endothelial cells [2]. Tumor necrosis factor-α is a powerful inducer of local inflammation in blood vessels, stimulates further activation of macrophages, induces secretion of matrix metalloproteinase-9 [3], and promotes expression of leukocyte adhesion molecules [4]. It affects lipid metabolism and may lead to hypertriglyceridaemia by decreasing lipoprotein lipase activity in cultured adipo­cytes [5]. High doses of cachectin are extremely toxic, and acute intravenous administration induces catabolic hormone release, tissue injury, and fatal shock [6,7].
The TNF-α locus is located within the human leukocyte antigen (HLA) class III gene cluster on the short arm of chromosome 6 [8]. The biallelic polymorphism with a G->α transition at position –308 occurs in the promoter region of the TNF-α gene, where the presence of guanine defines the common variant (TNFA1), whereas that of adenine defines the less common allele (TNFA2) [9]. The TNFA2 allele is a much more powerful transcriptional activator than the common allele, and is associated with high TNF-α production [10,11]. The persistence of TNF-α rather than peak levels predicts poor outcome in patients with acute coronary syndromes [12].
The present study assessed the genotype and allele frequency of the –308 (G->α) polymorphism in the promoter region of the TNF-α in male adults from Bashkor­tostan and looked for its possible association with myocardial infarction and sudden cardiac death (SCD) in individuals with atherosclerosis of the coronary artery.