Predictive value of cytokine gene polymorphisms for the development of end-stage renal disease.
BACKGROUND
Cytokines play a crucial role in different immunopathological conditions. Cytokine secretion is reported to be determined by polymorphisms in the cytokine genes. Since TNF-alfa and IL-10 are involved in regulation of inflammation, and TGF-beta 1 can induce fibrosis and renal insufficiency - dominant features of end-stage renal disease (ESRD), we explored the hypothesis that polymorphisms of these cytokine genes may be possible genetic susceptibility factors for the progression of renal failure.


METHODS
We studied the IL-10 (-1082), TNF-alfa (-308), TGF-beta 1 (codon 10;25) gene single nucleotide polymorphisms in 118 healthy donors and 103 patients with ESRD (44 hemodialysis patients with diabetic nephropathy and 59 hemodialysis patients with glomerulonephritis) using PCR-SSP.


RESULTS
Significant associations of ESRD with the TGF-beta 1 (codon 10) TT (odds ratio [OR] = 5.31; 95% confidence interval [95% CI], 3.77-7.02; p<0.001) and IL-10 (-1082) GG (OR=2.35; 95% CI, 1.67-3.15; p<0.01) genotypes were found. Statistical analysis of genotype frequencies made separately for the underlying renal disease (diabetes or glomerulo-nephritis) revealed the same linkage trend: TGF-beta 1 (codon 10) TT and IL-10 (-1082) GG were associated with type 2 diabetic nephropathy (p<0.001 and p<0.05, respectively) and chronic glomerulonephritis (p<0.001 and p<0.01, respectively). No significant differences in the TNF-alfa , TGF-beta 1 (codon 25) genotype distribution between healthy controls and patients with diabetic nephropathy- or glomerulonephritis-associated ESRD were detected.


CONCLUSIONS
Carriage of the TGF-beta 1 (codon 10) TT and IL-10 (-1082) GG genotypes may increase susceptibility to ESRD in German patients with type 2 diabetes or glomerulonephritis.
Babel
Nina
N
Department of Nephrology and Internal Intensive Care, Campus Virchow Clinic, Charité University Medicine, Berlin, Germany. nina.babel@charite.de
Gabdrakhmanova
Lelia
L
Hammer
Markus H
MH
Schoenemann
Constanze
C
Skrypnikov
Volodimir
V
Poliak
Nina
N
Volk
Hans-Dieter
HD
Reinke
Petra
P
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000150:complications / Q000235:genetics*; D005260:Female; D005858:Germany; D005921:Glomerulonephritis / Q000150:complications / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D016207:Cytokines