Association of Polymorphisms of the TNF-alpha and TGF-beta1 Genes with Renal Allograft Dysfunction / 대한이식학회지

ABSTRACT

PURPOSE: Tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 have been shown to play important roles in allograft rejection of various organs. This study was performed to evaluate the association of TNF-alpha and TGF-beta1 genes and renal allograft dysfunction. METHODS: Five TNF-alpha ( 1,031 T/C, 863 C/A, 857 C/T, 308 G/A, 238 G/A) and two TGF-beta1 (codon 10 T/C, codon 25 G/C) single nucleotide polymorphism (SNP) sites were studied using PCR-SSCP and PCR-RFLP methods in 100 controls and 165 patients underwent renal transplantation. For the TGF-beta1 gene, we also studied the polymorphism of donors. RESULTS: The allele frequencies of each SNP sites in controls were not different from those of patients. The phenotype frequency of TNF-alpha high producer type, 308 A was significantly higher in the patients with recurrent acute rejection episodes (REs) compared with patients with no or one RE (38.5% vs. 9.2%, P=0.007). The frequency of TGF-beta1 low producer genotype, codon 10 CC was also significantly higher in the patients with recurrent REs (53.8% vs. 22.4%, P=0.029). Analysis of chronic renal allograft dysfunction (CRAD) revealed that the TGF-beta1 high producer type, codon 10 T allele in donors was associated with CRAD (66.7% vs. 48.2%, P=0.043). This association was significant only among patients with recurrent REs. Occurrence of CRAD was not influenced by TGF-beta1 polymorphisms in the patients. CONCLUSION: These results would be useful for predicting high risk group for acute rejection or CRAD in renal transplantation and might be useful for implying individualized immunosuppressive therapy.