TNF-α polymorphisms and coronary artery disease: Association study in the Korean population

Coronary artery disease (CAD) results from atherosclerosis, a chronic inflammatory disease mediated in part by proinflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), which is expressed by atherosclerotic plaques. In this study, we investigated whether TNF-alpha gene promoter polymorphisms affect the incidence of CAD in Koreans by genotyping. 404 Control subjects and 197 patients who previously received a coronary artery stent for the G/A, C/T. and C/A polymorphisms at position -238, -857 and -863, respectively. The G/G, G/A and A/A genotypes at position -238 occurred in 85.8%, 14.2% and 0% CAD patients and 91.8%, 7.9% and 0.3% control subjects, respectively. The G/A polymorphisms at position -238 were significantly associated with CAD when assuming a dominant model of inheritance (OR = 1.87; 95% CI = 1.10-3.20; P = 0.02), and A allele carriers had a significantly increased risk of developing CAD relative to the G allele (OR = 1.74; 95% CI = 1.04-2.92; P = 0.03). However, the polymorphisms at positions -857 and -863 were not associated with CAD. Haplotype-based analysis revealed the CAD and control groups differed significantly in the frequencies of haplotype ACC at positions -238, -857 and -863 (OR = 1.77; 95% CI = 1.05-2.98; P = 0.03). This was confirmed by multivariate analysis after adjusting body mass index and the presence of diabetes and hypertension (OR = 2.06; 95% CI = 1.15-3.68; P = 0.015). Thus, the -238A allele of TNF-alpha is associated with an increased risk of CAD and could be used as predictor for CAD in Koreans. Further studies are needed to elucidate the clinical implications of these findings. (C) 2013 Elsevier Ltd. All rights reserved.