We found no association between the TNFa gene G(–308)A polymorphism and MI in our Slovene patients with DM2. This may be the first report of this negative association. The G(-308)A polymorphism has been related to MI [13], to unstable angina [16], and ST-elevation MI (STEMI) [20]. Other studies failed to demonstrate an association between this polymorphism and MI [12,14,15]. This discordance may be due to the multifactorial nature of the MI, to differences in study design or to genetic heterogeneity within and between the populations studied. Moreover, we found significantly higher serum TNFa levels in DM2 patients with the GG genotype than with AG genotype. Several environmental and genetical factors (i.e., age, cigarette smoking, ischemia) influence serum TNFa levels [9,21,22]. The G(–308)A polymorphism is most probably a functional polymorphism, since it has been reported to affect the serum TNFa levels [21,22]. The A allele was associated with decreased TNFa concentrations in offspring less than 18 years of age and males who were not overweight [BMI <25 kg/m (2)]. Moreover, cigarette smoking was reported to lower TNF concentrations, but in our study we did not find an effect of smoking on TNF concentration. It has been speculated that cigarette smoking abolishes TNFa cellular release from cells [21,22].

      We studied only DM2 patients who had experienced a MI 1-9 months earlier, and our results may be affected by survival bias. Moreover, the exclusion of CAD on the basis of a negative history of MI or angina pectoris, and absence of ischemic changes on electrocardiograms and during exercise stress testing, was disadvantaged by the possibility that some of the patients without MI may have experienced asymptomatic CAD. In a recent study, 18% of asymptomatic DM2 patients with a negative result of exercise stress testing, presented silent CAD with significant (³70%) angiographically-documented coronary stenosis [17]. In conclusion, the G(–308)A polymorphism of the TNFa gene is not a risk factor for MI with DM2 in Slo­venes of Slavic origin.