TNF‐α and TGF‐β1 gene polymorphisms and renal allograft rejection in Koreans

Abstract

This study was performed in order to evaluate the association of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) gene polymorphisms with renal allograft rejection in Koreans. Five TNF-alpha (-1031T/C, -863C/A, -857C/T, -308G/A and -238G/A) and two TGF-beta1 (codon 10 T/C and codon 25 G/C) single-nucleotide polymorphism (SNP) sites were studied by using polymerase chain reaction (PCR) single-strand conformation polymorphism and PCR restriction fragment length polymorphism methods in 100 controls and 164 patients. The patients underwent renal transplantation, having one or more Human leukocyte antigen (HLA)-A, HLA-B and HLA-DR antigens mismatched with their donors. For the TGF-beta1 gene, we also studied the polymorphism of donors. The allele frequencies of each SNP site in controls were not different from those of patients. The frequency of TNF-alpha high-producer genotype, -308GA, and TGF-beta1 lower (intermediate)-producer genotype, codon 10 CC and codon 25 GG, were significantly higher in patients with recurrent acute rejection episodes (REs), compared to those in patients with no or one RE. The highest risk group for developing recurrent REs showed the combination of TNF-alpha high- and TGF-beta1 lower-producer genotypes. Analysis of chronic renal allograft dysfunction (CRAD) revealed that TGF-beta1 high-producer genotype of donors, codon 10 TT/TC and codon 25 GG, is associated with CRAD especially in patients with recurrent REs. The highest risk group for developing CRAD showed the combination of recipient's TNF-alpha high- and donor's TGF-beta1 high-producer genotypes. These results would be useful for predicting high-risk group for acute rejection or CRAD in renal transplantation.

Single Nucleotide Polymorphisms of Cytokine Genes are Associated with Fibrosis of the Intrahepatic Bile Duct Wall in Human Clonorchiasis

“…The highproducing genotype, GA (9.6%) and the low-producing genotype, GG (90.4%) were detected at -308 G/A for TNF-αanaly-sis. The high-producing genotype, TC (55.0%) or TT (27.1%), and the low-producing genotype CC (17.9%) for TGF-β 1 were found at codon 10 T/C and the genotype GG only at codon 25 G/C (Table 2) [12]. This cytokine gene polymorphism data from Chinese subjects were similar to those seen in Koreans [11,12].…”

“…In our study on TNF-αthe lowproducing genotype produced more fibrosis than the high-producing genotype (63% vs 20%), and this indicates that TNF-α may suppress fibrosis in the liver. The genotypes and allelic frequencies of IFN-γ , IL-10, TNF-α , and TGF-β 1 genes in Chinese subjects were similar to those seen in Koreans [11,12], and based on these similarities the genotype polymorphisms associated with clonorchiasis were also expected to be similar to those in Koreans.…”

“…In several liver diseases, low-producing IL-10 and high-producing IFN-γand TGF-β 1 genotypes are known to promote hepatic fibrosis, but the action of TNF-αis unclear [10]. Similarly, rejection in kidney transplantation was reported to occur more frequently among individuals with high risk IFN-γand TNF-αgenotype combinations than those of moderate or low risk genotypes [12].…”

“…However, a significant correlation was observed when the cytokine genotypes of IFN-γand TNF-αwere grouped in combination according to the risks for fibrosis [11,12]. Among individuals with clonorchiasis of EPG ≥ 300, the high risk group, intermediate-producing IFN-γ(+874AT) and low-producing TNF-α(-308GG) genotypes, was significantly correlated with development of IHDD (Table 5), but not with that of PDE.…”

Association of pro/anti-inflammatory cytokine gene variants in renal transplant patients with allograft outcome and cyclosporine immunosuppressant levels

“…The other combination of TNF-α (-308) with TGF-B projecting recipients with TNF-α 308/high -TGF-β C-del/low associated with higher risk of rejection. Our observations suggested that high producing genotypes of proinfl ammatory cytokine TNF-α and low producing genotypes of TGF-β (anti-infl ammatory) may have a major impact on the immune response responsible for allograft acceptance/rejection (Park et al 2004).…”