TGF-beta(1) Genotyping in Kidney Transplantation

Jeon, Dong Seok

Abstract

BACKGROUND
Transforming growth factor-beta1 (TGF-beta(1)) is a multifunctional cytokine that is involved in the development of the features of chronic rejection in organ transplantation, namely fibrosis. The severity and frequency of the rejection are dependent on the amount of the TGF-beta(1) production. The level of TGF-beta(1) synthesis varies between individuals and is dependent on varieties of single nucleotide polymorphism (SNP) in the genes encoding TGF-beta(1). The goal of this study was to determine TGF-beta(1) genotypic variations in Koreans primarily related to kidney transplantation since most of the studies dealt with lung transplantation in Caucasoid populations.
METHODS
From January to June 1999, samples were collected from 98 patients and donors for kidney trans plantation. The sample were genotyped by polymerase chain reaction using sequence specific primer (PCR-SSP) for six known SNPs in the TGF-beta(1) gene: -988, -800, -509 and codon 10, 25 and 263. All procedures of PCR were performed under the same conditions.
RESULTS
Only 3 genotypes of -988/-800/-509, codon 10 and 25 in exon 1 and codon 263 in exon 5, were identified: LL type, CGC/CGC-leucine/leucine (L/L)-arginine/arginine (A/A)-threonine/threonine (T/T); LP type, CGC/CGT-leucine/proline (L/P)-AA-TT; PP type, CGT/CGT-PP-AA-TT. Homozygosity for arginine at codon 25 and threonine at codon 263 were found in 100% of the patients.
CONCLUSIONS
Even though it was stated that polymorphisms in the TGF-beta(1) gene, especially at codon 25, were highly related in the production of TGF-beta(1) and also the frequency of graft rejection, as stated in English literature, and 100% of arginine homozygosity at codon 25 showed in this study. Therefore, there might be an another factor influencing the graft rejection and fibrosis other than TGF-beta(1) genotype unless the TGF-beta(1) level of serum has been found to be higher or if there have been more frequent rejections in Koreans. Confirmation of this prediction needs proper comparisons between genotyping, TGF-beta(1) level and chronic rejection in more patients in the near future.