Transforming growth factor beta 1 gene variants increase transcription and are associated with liver cirrhosis in Chinese.
OBJECTIVE
Transforming growth factor beta1 (TGFbeta1) acts as an important profibrogenic cytokine in liver fibrogenesis. The aim of this study was to explore the association between TGFbeta1 gene polymorphisms and liver cirrhosis.


METHODS
Totally 118 Chinese suffering from liver cirrhosis induced by HBV infection and 104 healthy controls were recruited. The polymorphisms at positions -988, -800, -509 and codon10, codon25, codon263 of the TGFbeta1 gene were genotyped by ARMS-PCR or LightCycler. Enzyme immunoassay was used for TGFbeta1 measurement. The promoter activities and DNA-binding capacities containing -509C>T were analyzed by reporter gene and EMSA.


RESULTS
The allele frequencies of CAT -509 and of T at codon10 were elevated in patients at severe Child-Pugh grade. Elevated concentrations of TGFbeta1 were observed in patients, especially in those with -509CC/CT and codon10 TT/TC. Flanking sequences containing -509C showed higher promoter activities than -509T. EMSA showed one nucleotide change at -509C>T influenced nuclear protein binding to the putative binding site.


CONCLUSIONS
The C allele at -509 and the T allele at codon10 could play important roles in progression of liver cirrhosis. The C allele at -509 mediates higher transcriptional activity than the T allele providing a potential explanation for the clinical findings.
Department of Laboratory Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Hao
H
Wang
Yun-Peng
YP
Zhao
Chun-Fang
CF
Gao
Qiang
Q
Ji
Axel M
AM
Gressner
Zai-Xing
ZX
Yang
Ralf
R
Weiskirchen
D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002460:Cell Line; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D041681:NIH 3T3 Cells; D017354:Point Mutation; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D053773:Transforming Growth Factor beta1