J Korean Soc Transplant.  2002 Jun;16(1):38-46.

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

• Park JY
• Park MH
• Park HJ
• Ha J
• Kim SJ
• Ahn C

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.

Keyword

TNF-alpha; TGF-beta1; Polymorphism; Acute rejection; Chronic allograft dysfunction

MeSH Terms

Alleles
Allografts*
Codon
Gene Frequency
Genotype
Humans
Kidney Transplantation
Phenotype
Polymorphism, Single Nucleotide
Tissue Donors
Transforming Growth Factor beta1*
Transforming Growth Factors
Tumor Necrosis Factor-alpha*
Codon
Transforming Growth Factor beta1
Transforming Growth Factors
Tumor Necrosis Factor-alpha