Genetic analysis of human predisposition to hepatosplenic disease caused by schistosomes reveals the crucial role of connective tissue growth factor in rapid progression to severe hepatic fibrosis

Pathol Biol (Paris). 2013 Jan;61(1):3-10. doi: 10.1016/j.patbio.2013.01.005. Epub 2013 Feb 12.

Abstract

Schistosome worms inhabit mammalian mesenteric veins. Their eggs cause chronic inflammation, which progresses to periportal fibrosis in 5 to 30% of cases, increasing portal blood pressure and leading to esophageal varices. Episodes of bleeding cause hepatic necrosis and may ultimately lead to hepatic failure and the death of the patient. Schistosome infections can also cause pulmonary hypertension and heart failure. The mechanisms of fibrogenesis and fibrolysis are beginning to be unraveled, but it remains unclear why disease occurs only in certain subjects, as also observed for other types of chronic liver inflammation, as in hepatitis C or B. We summarize here the results that showed that fibrosis progression is determined by a genetic locus on chromosome 6. The CCN2 gene at this locus, encodes CTGF that is a crucial regulator of fibrosis. Two groups of CCN2 polymorphisms independently modulate the progression of hepatic fibrosis. These results were obtained in an Asian population, but were extended to humans living in Africa and South America and are presently tested in liver fibrosis of other etiological origins.

MeSH terms

  • Animals
  • Asian People / genetics
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / physiology*
  • Disease Progression
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Liver Cirrhosis / ethnology
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / parasitology
  • Liver Diseases, Parasitic / ethnology
  • Liver Diseases, Parasitic / etiology
  • Liver Diseases, Parasitic / genetics*
  • Schistosoma / physiology
  • Schistosomiasis / complications
  • Schistosomiasis / ethnology
  • Schistosomiasis / genetics*
  • Severity of Illness Index
  • Splenic Diseases / ethnology
  • Splenic Diseases / etiology
  • Splenic Diseases / genetics*
  • Splenic Diseases / parasitology

Substances

  • CCN2 protein, human
  • Connective Tissue Growth Factor