We have compared the allele frequencies of the –308 (G->α) polymorphism of the TNF-α gene with published data for some other population groups [17-23]. In our control group, the genotype frequencies of the –308 (G->α) polymorphism of the TNF-α gene were similar to those reported in the other control groups (Table 2) but significantly different from those found in Japanese (p <0.001). We also analyzed the possible association of this polymorphism and the two clinically important manifestations of atherosclerosis, namely MI and SCD.

Recent reports have suggested that the –308 (G->α) polymorphism of the TNF-α gene did not contribute to acute MI [19,20,24] or CAD [20,25], and that it was associated with neither single vessel CAD nor multi vessel CAD [12]. Nevertheless, some reports have found an association of the TNFA2 allele with parental history of MI [24] and obesity [19]. We found no association of the –308 (G->α) polymorphism of the TNF-α gene with MI.
Tumor necrosis factor-α has been shown to be capable of inducing an increased plasma level of the catecholamines, and it is a powerful inducer of acute hypodynamic shock and severe tissue injury in animals [7]. It causes hypotension, metabolic acidosis, and death within minutes to hours after intravenous infusion in animals [6,7]. Tumor necrosis factor-α has also been implicated as a mediator of cardiac dysfunction [7]. Because of these effects of TNF-α, we hypothesized that the –308 (G->α) mutation in the promoter region of the TNF-α may be a marker of in­creased predisposition to SCD. This polymorphism was not associated with atherosclerosis of the coronary artery in an autopsy study of Finnish men [18] who had experienced sudden unexpected death or death suspected to be caused by violence. In our study, the reason was only SCD due to CAD. For group B we found no association of this polymorphism with SCD when compared with control group, but the frequencies of the TNFA2 allele and TNFA1/2 genotype in the SCD group were significantly higher than in the MI patients. There were no significant differences for the TNFA2/2 genotype. But because this may be due to the small number of individuals, we combined the homozygous and heterozygous subjects into one group and found that the genotype frequencies in this group were significantly higher than in the same group with MI. Thus, we consider that the higher frequency of TNFA2 in individuals with SCD compared with the MI patients emphasizes the important role of TNFA2, which is correlated with higher TNF-α plasma concentration in the pathogenesis of SCD in men with atherosclerosis of coronary arteries.
In summary, this study shows that –308 (G->α) polymorphism in the promoter region of the TNF-α gene is not associated with MI or SCD in the male population from Bashkortostan, but may be a marker of SCD in patients with coronary artery disease.

Table 2. Genotype frequencies (%) of the –308 (G®A) polymorphism of the TNF-a gene in healthy control subjects from Russia (Ufa, Bashkortostan) and those from other populations.