174 G/C interleukin 6 genotype is related to higher risk of graft loss and GFR decline in 5-year observation in kidney graft recipients
U Siekiera, J Chudek, A Kolonko, M Szotowska, H Karkoszka, L Cierpka, A Więcek
Ann Transplant 2009; 14(1): 38-38
Background: Polymorphisms of TNF-alfa, IL-10, IL-6, IFN-gamma and TGF-b1
genes are related to the constitutional gene expression and production of appropriate cytokines. The aim of this study was to assess the impact of TNF-alfa, IL-10, IL-6, and IFN-gamma genotypes on GFR and long-term kidney graft outcome.
Material/Methods: Genotyping was performed in 240 subsequent kidney graft recipients from 1998 to 2002. Genomic DNA was obtained from peripheral leukocytes. Identification of cytokine genotypes was based on PCR-SSP method for TNF-alfa at position -308 A/G, IL-10 at positions -1082 A/G, -819 T/C, -592 A/C, IL-6 at position -174 G/C, IFN-gamma at position +874 T/A and TGFb1in codon 10 (T/C) and 25 (G/C). Genotypes were grouped according to the strength of cytokines expression. Nineteen patients with primary graft nonfunction were excluded from the analysis. During 5-year follow up period 17 patients died with functioning graft and 35 patients developed graft failure. Glomerular filtration rate (eGFR) was estimated based on MDRD equation. The yearly eGFR decline was calculated from 6 months to 5 years follow-up period.
Results: Only IL-6 gene polymorphism had signifi cant impact on kidney graft
survival and decline of eGFR. In patients with CC genotype (determining low IL-6 production) only 6 out of 68 patients (8.8%) lost kidney graft while in the group with GG and GC genotypes (determining higher IL-6 production) 29 out of 151 patients (19.2%). The risk of graft loss (hazard ratio) was 2.38 (1.01-4.16), p=0.046 for GG or GC carriers. The frequency of death was
similar in both groups (7.3 and 7.9%). eGFR decline was significantly faster
in GG or GC carriers [-4.61 (-6.01- -3.21) ml/min/year] than CC carriers
[-2.07 (-3.27- -0.88) ml/min/year], p=0.02.
Conclusions: IL-6 genotypes of the kidney recipient, determining higher IL-6
constitutional expression, are related to the increased risk of graft loss.
Keywords: Kidney Transplantation