PURPOSE:We investigated the association of a polymorphism within the promoter of TauNuF-alpha locus at the position -308 on the likelihood of having acute coronary syndromes (ACS) in Greek adults. METHODS:We studied demographic, lifestyle, and clinical information in 237 hospitalized patients (185 males) with a first event of an ACS and 237 matched by age and sex (controls) without any clinical evidence of coronary heart disease. Genotyping was performed by PCR-RFLP analysis. RESULTS:The genotype frequencies were in patients, 87% (n = 206), 12% (n = 29), and 1% (n = 2) for G/G, G/A, and A/A, and in controls, 96% (n = 227), 4% (n = 10), and 0% (n = 0) for G/G, G/A, and A/A, respectively (P = 0.04). After adjusting for age and sex, as well as various potential confounders, we observed that G/A or A/A genotypes were associated with 1.94-fold higher odds (95% CI 1.06 to 3.68) of ACS compared to G/G homozygotes. No gene to-gender or to-clinical syndrome interactions were observed. Further subgroup analysis showed that the distribution of TNF-alpha -308G>A polymorphism was associated with the presence of family history of CHD in patients, but not in controls. In particular, in G/A and A/A patients 17.2% reported family history of CHD, whereas in G/G patients, 34.5% reported family history (P = 0.036). CONCLUSIONS:Our findings may state a hypothesis of an association between the -308G>A TNF-alpha polymorphism the development of ACS and the presence of family history of CHD, in Greece.