title: Association between gene polymorphisms of connective tissue growth factor and the progression of chronic liver disease associated with hepatitis C.
abstract: OBJECTIVE
  Fibrogenic cytokines, such as transforming growth factor-beta 1 play a central role in the progression of liver fibrosis. Recently, functional gene polymorphisms in these cytokines have been identified, and some reports have validated the presence of associations between these polymorphisms and disease progression. Connective tissue growth factor (CTGF) is a stimulating factor for fibroblast proliferation and matrix production. This study aimed to examine the relationship between CTGF gene polymorphisms and the progression of hepatitis C virus (HCV)-related chronic liver disease, as well as the incidence and prognosis of hepatocellular carcinoma (HCC).
  
  
  METHODS
  A review was conducted among 235 HCV patients (117 patients with chronic hepatitis (CH) and 118 patients with liver cirrhosis (LC)). The CTGF gene polymorphism (rs6918698; -945 G/C) was identified according to the chimeric cycling probe method. The rate of liver fibrosis progression was measured using two liver fibrosis prediction formulas, the Forns index and the FibroIndex. All HCC patients were followed regularly every month.
  
  
  RESULTS
  The frequency of the -945 C allele was higher among the LC patients than the CH patients. Regarding the rate of liver fibrosis progression over five years, C homozygotes tended to exhibit a faster rate than G carriers, although the difference was not significant. Among the LC patients, the C homozygotes demonstrated lower prothrombin times, higher rates of indocyanine green retention and higher Child-Pugh scores than the G carriers. There were no significant tendencies in the genotype distribution, irrespective of the status of HCC. However, the prognosis of HCC was poorer for the C homozygotes than for the G carriers.
  
  
  CONCLUSIONS
  A CTGF -945 C homozygote status is a significant risk factor for the progression of HCV-related chronic liver disease, including HCC.
authors.affiliation: Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, Tottori University School of Medicine, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ikebuchi
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ishida
authors.forename: Kinya
authors.initials: K
authors.lastname: Okamoto
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Murawaki
mesh_terms: D000368:Aged; D000483:Alleles; D055513:Connective Tissue Growth Factor / Q000235:genetics* / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis
chemical_list: D004279:DNA, Viral; D055513:Connective Tissue Growth Factor