Background and objective: Tumor necrosis factor-alpha (TNFalpha) is a potent proinflammatory cytokine. Through its effects on lipid metabolism and endothelial function, TNFalpha is involved in cardiovascular disease (CVD). We have studied two polymorphisms in the promoter region of the TNFalpha gene (TNF -308G/A and TNF -238G/A) in end-stage renal disease (ESRD) patients with and without CVD. The aim was to assess the association of these polymorphisms with ESRD and cardiovascular comorbidity in hemodialyzed patients.
Methods: A total of 603 patients with ESRD treated with hemodialysis (382 patients with CVD) and 325 healthy control subjects were genotyped for the TNF -308G/A and TNF -238G/A ploymorphisms by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure.
Results: The A allele of the TNF -308 polymorphism was more frequent in the ESRD group than in control individuals. The odds ratio (OR) for the risk allele was 2.05 (95% CI 1.48, 2.84). In the subgroup of ESRD patients with CVD, the OR was 5.76 (95% CI 3.67, 9.03) relative to ESRD patients without CVD. There was no association observed between the TNF -238 polymorphism and renal failure or CVD in ESRD patients.
Conclusion: Our results demonstrate for the first time that the A allele of the TNF -308 polymorphism is associated with CVD in hemodialyzed ESRD patients. If confirmed in prospective studies, it may be a predictor of increased susceptibility to CVD in these patients.