TNF alpha-308 genotype and renin-angiotensin system in hemodialysis patients: An effect on inflammatory cytokine levels?

Abstract

Background: Renin-angiotensin system (RAS) was suggested to modulate inflammatory cytokine production. Angiotensin II was consistently shown to increase production of tumor necrosis factor alpha (TNF-α). However, inflammatory cytokines and RAS were modulated by genetic polymorphisms such as TNF-α-308 G > A and angiotensin-converting enzyme (ACE) I/D gene polymorphisms. The aim of this study was to investigate the effects of ACE and TNF-α genotypes on inflammatory cytokines in hemodialysis (HD) patients. Methods: ACE I/D and TNF-α-308 G > A genotypes, pre- and postdialysis plasma renin activity (PRA), serum ACE, interleukin-1 beta (IL-l), and TNF-α levels were determined in 22 HD patients. Results: Predialysis serum ACE activity is correlated with TNF-α (r = 0.63; P = 0.01), and PRA was correlated with IL-l levels (r = 0.49; P = 0.02). Pre/postdialysis IL-l and TNF-α were similar in DD and II/ID ACE genotypes. Pre-dialysis TNF-α and IL-l (32.4 + 5; 35.1 + 4.2 vs. 28.1 + 3.7; 26.5 + 6.2 pg/mL; P < 0.05) and postdialysis TNF-α levels (30.4 + 1.4 vs. 28.4 + 0.82 pg/mL; P < 0.05) were significantly higher in TNF1/2 than TNF1/1 patients. Conclusion: ACE and TNF-a-308 G>A (1/2) gene polymorphisms may contribute to modulation of proinflammatory cytokine production and hence chronic inflammation in HD patients. © 2005 International Center for Artificial Organs and Transplantation.