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


CONCLUSIONS
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.
Genctoy
Gultekin
G
Department of Internal Medicine, Division of Nephrology Hacettepe University Faculty of Medicine, Ankara, Turkey.
Altun
Bulent
B
Kiykim
Ahmet Alper
AA
Arici
Mustafa
M
Erdem
Yunus
Y
Cağlarg
Meltem
M
Yasavul
Unal
U
Turgan
Cetin
C
Cağlar
Sali
S
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic; D006435:Renal Dialysis; D012084:Renin-Angiotensin System / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007703:Peptidyl-Dipeptidase A