Polymorphisms within the tumor necrosis factor locus and prevalence of coronary artery disease in middle-aged men

Tumor necrosis factor (TNF) is an important cytokine in the inflammation pr ocess of atherosclerosis and is also involved in lipid metabolism. Two bial lelic polymorphisms within TNF gene locus-TNFA at the position - 308 in the promoter region of the TNF gene and TNFB in the first intron of the lympho toxin-alpha (LT-alpha) have been reported to be associated with TNF product ion and with susceptibility to inflammatory diseases. We studied the associ ation of these polymorphisms within the major histocompatibility complex (M HC) III region with coronary atherosclerosis and its manifestations. The au topsy series comprised 700 Caucasian Finnish men, aged 33-70 years (The Hel sinki Sudden Death Study). Coronary stenosis and surface area of atheroscle rotic changes (fatty streaks. fibrous plaques, complicated lesions and calc ification) were measured and the presence of myocardial infarction and coro nary thrombosis recorded. TNFA and TNFB genotypes were determined by the PC R-RFLP technique. The allele frequencies were TNFA1/TNFA2 = 0.88/0.12 and T NFB1/TNFB2 = 0.30/0.70. There was a strong linkage disequilibrium between t he two polymorphisms. There were no differences in coronary stenosis and in the frequency of old or recent myocardial infarction or coronary thrombosi s between men with different genotype status in either locus. Men with TNFA 22 or TNFB11 genotype tended to have more fibrous lesions and calcification in their coronary arteries. TNFA and TNFB polymorphisms are unlikely to co ntribute to progression of atherosclerosis in a way clinically important. ( C) 2001 Elsevier Science Ireland Ltd. All rights reserved.