Transforming growth factor-beta1 gene polymorphisms are associated with progression of liver fibrosis in Caucasians with chronic hepatitis C infection.
OBJECTIVE
Considerable attention is focused on polymorphisms in the gene encoding transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine that is in turn a potent growth inhibitor involved in wound healing and differentiation. In humans, it promotes the pathogenesis of organ fibrosis, atherosclerosis, cancer, autoimmune and inflammatory diseases, keloid disease, and hypertrophic scarring. For this reason, much emphasis has been placed on studies elucidating the impact of TGF-beta1 and its gene variations for the susceptibility and pathogenesis of these diseases. Unfortunately, some studies have serious limitations.


METHODS
We have recently described a high-throughput method for investigation the Arg25Pro polymorphism of human TGF-beta1 gene and showed that the frequency of the Pro25 allele is significantly associated with hepatic fibrogenesis. In this report, we describe two novel LightCycler (LC) techniques that facilitate the examination of the two other known alterations in the coding region of TGF-beta1. We investigated whether these polymorphisms contribute to hepatitis-induced progression of fibrogenesis in Chinese and Caucasians.


RESULTS
In the Chinese ancestry, the gene polymorphisms at codons 25 and 263 were not found and the genetic variant at codon 10 is unlikely to confer susceptibility to hepatic fibrosis. Contrarily, in Caucasians TGF-beta1 allelic variations are more frequent and the presence of prolines either in codon 25 or 10 is associated with the interindividual variability in developing more severe fibrosis during chronic hepatitis C infection.


CONCLUSIONS
In summary, these results confirm the hypothesis that TGF-beta1 polymorphisms are associated with fibrosis progression in Caucasians chronically infected with hepatitis C.
Wang
Hao
H
Department of Laboratory Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Mengsteab
Senait
S
Tag
Carmen-G
CG
Gao
Chun-Fang
CF
Hellerbrand
Claus
C
Lammert
Frank
F
Gressner
Axel-M
AM
Weiskirchen
Ralf
R
D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000208:ethnology* / Q000235:genetics* / Q000821:virology; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D044465:White People / Q000235:genetics*
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1