Transforming growth factor beta 1 : Role in the progression of chronic renal failure.

TGF-beta1 plays an important role in the pathogenesis of experimental and clinical glomerulosclerosis and tubufointerstitial fibrosis. Associations have been described between polymorphisms of cytokine and growth factor genes and susceptibility to, or progression of, an increasing number of diseases. In this study, single nucleotide polymorphisms (SNPs) in the TGFbeta1 gene were investigated as possible markers for the progression of chronic renal failure (CRF). One hundred and forty two Caucasian patients with CRF were screened for four TGFB1 SNPs: T-509C in the promoter region; Arg25Pro and Leu10Pro in exon 1 and Thr263Ile in exon 5. There were significant differences between CRF patients and controls in allele frequencies of two of the SNPs (Leu10Pro and C-509T), indicating an association with susceptibility to CRF, We also observed a significant association between rate of progression of CRF (the slope of the reciprocal of serum creatinine v time) and genotype, both at codon 25 (odds ratio 3.77, 95% confidence interval, 2.2 - 6, p <0.001) and at the -509 promoter site (odds ratio 1.67, 95% confidence interval 1.1-2.5), p <0.005) in patients with primary nephropathy (excluding PKD). Genotype at codon 25 was also associated with severity of proteinuria (p= 0.038), plasma TGF-B1 protein levels (p = 0,01), and the severity of glomerulosclerosis (p<0.05). Genotype at C-509T was associated with the level of renal tubular TGF-B1 immunostmning (p = 0.0006) and with renal interstitial inflammatory cellular infiltration (p=0,015). There was a highly significant correlation between the degree of cellular infiltration in renal tissues and tubular TGF-beta1 immunostaining.