A functional variation in CHI3L1 is associated with severity of liver fibrosis and YKL-40 serum levels in chronic hepatitis C infection

J Hepatol. 2009 Feb;50(2):370-6. doi: 10.1016/j.jhep.2008.09.016. Epub 2008 Dec 4.


Background/aims: YKL-40 is a chitinase-like protein involved in matrix remodelling and a non-invasive fibrosis marker. We assessed whether a functional promoter polymorphism in CHI3L1, encoding YKL-40, is associated with HCV-induced liver fibrosis and influences YKL-40 serum concentrations.

Methods: The CHI3L1 -131G-->C promoter polymorphism was genotyped in two cohorts of HCV infected patients (n=440) by 5'-endonuclease assays. Histological fibrosis scores and YKL-40 serum levels (ELISA) were associated with CHI3L1 -131G-->C by quantitative and qualitative genetic analyses and corrected by multivariate analysis.

Results: CHI3L1 -131G-->C genotype was strongly associated with the stage of liver fibrosis in the screening (n=265, P=0.001) and validation cohort (n=175, P=0.009). Homozygous carriers of the G allele were protected from severe fibrosis (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of YKL-40 in HCV infected patients (P=0.002).

Conclusions: The CHI3L1 promoter polymorphism -131G-->C determines YKL-40 serum levels and is associated with the severity of HCV-induced liver fibrosis. These results suggest a functional role of YKL-40 in liver fibrogenesis and should be taken into account when using YKL-40 as a non-invasive fibrosis marker.

MeSH terms

  • Adipokines
  • Adult
  • Chitinase-3-Like Protein 1
  • Female
  • Glycoproteins / blood*
  • Glycoproteins / genetics*
  • Glycoproteins / physiology
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / genetics
  • Humans
  • Lectins
  • Liver Cirrhosis / etiology*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • RNA, Messenger / analysis


  • Adipokines
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Glycoproteins
  • Lectins
  • RNA, Messenger