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

Artif Organs. 2005 Feb;29(2):174-8. doi: 10.1111/j.1525-1594.2005.29029.x.

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-alpha). However, inflammatory cytokines and RAS were modulated by genetic polymorphisms such as TNF-alpha-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-alpha genotypes on inflammatory cytokines in hemodialysis (HD) patients.

Methods: ACE I/D and TNF-alpha-308 G > A genotypes, pre- and postdialysis plasma renin activity (PRA), serum ACE, interleukin-1 beta (IL-1beta), and TNF-alpha levels were determined in 22 HD patients.

Results: Predialysis serum ACE activity is correlated with TNF-alpha (r = 0.63; P = 0.01), and PRA was correlated with IL-1beta levels (r = 0.49; P = 0.02). Pre/postdialysis IL-1beta and TNF-alpha were similar in DD and II/ID ACE genotypes. Predialysis TNF-alpha and IL-1beta (32.4 +/- 5; 35.1 +/- 4.2 vs. 28.1 +/- 3.7; 26.5 +/- 6.2 pg/mL; P < 0.05) and postdialysis TNF-alpha 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-alpha-308 G > A (1/2) gene polymorphisms may contribute to modulation of proinflammatory cytokine production and hence chronic inflammation in HD patients.

MeSH terms

  • Adult
  • Cytokines / biosynthesis*
  • Cytokines / blood
  • Female
  • Genotype
  • Humans
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / immunology
  • Polymorphism, Genetic
  • Renal Dialysis*
  • Renin-Angiotensin System / genetics
  • Renin-Angiotensin System / immunology*
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Peptidyl-Dipeptidase A