Association of polymorphisms of the transforming growth factor-β1 gene with the rate of progression of HCV-induced liver fibrosis

• Published in: Clinica chimica acta 2002, Vol.316 (1), p.83-94
• Main Authors: Gewaltig, Jan, Mangasser-Stephan, Kerstin, Gartung, Carsten, Biesterfeld, Stefan, Gressner, Axel M
• Format: Article
• Language: English
• Subjects: ARMS-PCR; Biological and medical sciences; Cytokine; Fibrosis; Genotyping; Human viral diseases; Infectious diseases; Medical sciences; METAVIR-score; TGF-β1 polymorphisms; Viral diseases; Viral hepatitis
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/S0009-8981(01)00738-0

Background: The objective of the present study was to elucidate possible relationships between four polymorphisms of the TGF-β1 gene (−800G>A; −509C>T; Leu10Pro; Arg25Pro) and stage, histological activity grade and progression rate of liver fibrosis, classified according to the METAVIR-score. Methods: Three study groups, i.e. 48 patients with hepatic fibrosis (26 with known duration of hepatitis C virus infection), 47 patients with non-fibrotic diseases and 50 healthy blood donors, were analyzed for TGF-β1 polymorphisms using ARMS-PCR and sequence analysis. The concentrations of total TGF-β1 in plasma and of hyaluronan, P-III-NP and activities of transminases in serum were measured. Results: The presence of proline at codons 10 and/or 25 was associated with a faster progression of fibrosis than other polymorphisms. Patients with the genotype 25ArgPro developed fibrosis significantly faster (0.23 units/year) than those having 25ArgArg (0.08 units/year). Similarly, the fibrosis progression rate of patients with genotypes 10LeuPro and 10ProPro was almost three times as fast as of those having genotype 10LeuLeu. Stage and histological activity grade of fibrosis in 25ArgPro in comparison to 25ArgArg were higher. Also 10LeuPro showed a higher average stage of fibrosis than 10LeuLeu. The TGF-β1 plasma concentrations of patients with hepatic fibrosis were not significantly different between carriers of 25ArgArg and 25ArgPro genotypes. The frequency of the genotype 25ArgPro in liver fibrotic patients was about three times that of the control group whereas the frequency distribution of the genotype 25ArgArg tended to lower frequency in the fibrosis group. TGF-β1-promoter polymorphisms did not show any correlation with stage, grade or progression of liver fibrosis. Conclusion: Our results indicate that the heterozygous ArgPro of codon 25 predicts significantly faster fibrotic progression of chronic hepatitis C than the homozygous 25ArgArg genotype. The homozygous LeuLeu genotype of codon 10 showed a slow progression of fibrosis.