Association of TNF-α serum levels and TNFA promoter polymorphisms with risk of myocardial infarction

Elevated levels of tumor necrosis factor-alpha (TNF-α), and presence of polymorphisms of the TNFA gene have been implicated in cardiovascular disease pathogenesis. We explored the relationship between polymorphisms in the TNFA gene (-1031C/T, -863C/A -857T/C, -308G/A, -238G/A), protein levels of TNF-α and their association to myocardial infarction (MI) using a sample of 1213 post-MI patients and 1561 healthy controls. MI risk was higher among men with elevated TNF-α levels, with the highest compared to the lowest TNF-α quartile giving a 70% risk increase (OR [95% CI]: 1.7 [1.1; 2.6]). Obese subjects who also had elevated TNF-α levels were at even higher risk for MI (OR [95% CI]: 3.4 [2.1; 5.6]). Higher TNF-α levels were seen among smokers (but not among non-smokers) carrying the -857T allele. Furthermore, a rare haplotype occurred more frequently among the cases than the controls. Elevated TNF-α levels are associated with increased MI risk. Obese subjects with elevated TNF-a levels, and carriers of polymorphisms in or near TNFA are particularly susceptible to the hazards of smoking, results which may have implications for cardiovascular preventive measures.