Coronary artery disease (CAD) is the leading cause of death in the European Union and in the rest of the developed world [1,2]. Atherosclerosis is generally accepted as a chronic inflammatory condition [3] and growing evidence indicates an important role of chronic inflammation in type 2 diabetes mellitus (DM2) [4]. The pro-inflammatory cytokines may play a central role in the pathogenesis of both CAD and DM2 [3]. An important pro-inflammatory cytokine is tumor necrosis factor a (TNFa) promotes inflammation and signals leading to cell death. It is produced by macrophages, mastocytes, lymphocytes, endothelial cells, and adipocytes [5]. With interleukins (IL) 1 and 6 it has a key role in inflammatory and immune reactions [6]. The TNF plasma concentrations increase in patients affected with premature CAD and is involved in obesity and insulin resistance [7-9], and its expression is regulated at the transcriptional level [10].           

  The TNFa gene is located on the short arm of chromosome 6 (p21.1-21.3) between the class I and class II regions of the HLA complex. A polymorphism that affects its transcription has been identified in the promoter region of the gene, a guanine-to-adenosine transition at –308 bp in the promoter region (termed the A allele). In some studies but not in others, an association between this polymorphism and CAD was demonstrated [12-16]. Since this polymorphism has not been tested as a potential marker of MI in DM2, we investigated whether it is associated with increased serum levels of TNFa, and whether it is associated with increased risk for MI in patients.