Assoziation zwischen vier Polymorphismen des menschlichen Transforming-Growth-Factor-beta1-Gens und der zeitlichen Progression der posthepatitischen Leberfibrose
Background: The objective of the present study was to elucidate possible relationships between four polymorphisms of the TGF-beta1 gene (-800G>A; -509C>T; Leu10Pro; Arg25Pro) and stage, histological activity grade and progression rate (METAVIR-score) of liver fibrosis. 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-beta1 polymorphisms using ARMS-PCR and sequence analysis. The concentrations of total TGF-beta1 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-1 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-beta1-promoter polymorphisms did not show any correlation with stage, grade or progression of liver fibrosis. Conclusion: The 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.
info:eu-repo/classification/ddc/610, Medizin, Leber, Fibrose, PCR, Polymorphismus, TGF-beta
Networked Digital Library of Theses and Dissertations
Publikationsserver der RWTH Aachen University