A polymorphism in the promoter of the tumor necrosis factor-α gene (−308) is associated with coronary heart disease in type 2 diabetic patients

Abstract

Background: Tumor necrosis factor-α (TNF-α) is a key cytokine in the inflammation process of atherosclerosis. Through its effects on lipid metabolism, insulin resistance and endothelial function, it might be involved in coronary heart disease (CHD). A biallelic polymorphism within the promoter of TNF-α locus at the position −308 has been reported to be associated with TNF production. We have studied the association of this polymorphism with CHD in a Mediterranean non-diabetic and type 2 diabetic population. Methods: Three hundred and forty one CHD patients (106 with type 2 diabetes), 207 healthy matched control subjects and 135 type 2 diabetic patients without CHD were evaluated. A single nucleotide polymorphism at the promoter TNF-α (−308) was analyzed by RFLP-PCR. Results: TNF-α (−308) genotype and allele frequencies for A carriers were higher in CHD patients than those observed in the control group (32.3 vs. 23.2%, P=0.03; and 18.8 vs. 12.1%, P=0.0047; respectively) independently of other risk factors. Genotypic analysis revealed that CHD patients with type 2 DM displayed a greater prevalence of the −308 TNF-α A allele (40.6%) than controls (23.2%) or CHD patients without type 2 DM (28.5%) ( P=0.0056). The odds ratio for CHD in type 2 diabetic patients in presence of −308 TNF-α A allele was 2.86 (CI 95%: 1.55–5.32). This difference was observed mainly in diabetic women for the A allele carriers (OR: 4.29; CI 95%: 1.6–11.76). Conclusions: These results suggest that −308 TNF-α gene polymorphism may contribute to CHD risk in patients with type 2 diabetes and it could constitute an useful predictive marker for CHD in type 2 diabetic women.