title: A functional variation in CHI3L1 is associated with severity of liver fibrosis and YKL-40 serum levels in chronic hepatitis C infection.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine III, University Hospital Aachen, RWTH Aachen, Pauwelsstr. 30, D-52057 Aachen, Germany.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Berres
authors.forename: Sven
authors.initials: S
authors.lastname: Papen
authors.forename: Katrin
authors.initials: K
authors.lastname: Pauels
authors.forename: Petra
authors.initials: P
authors.lastname: Schmitz
authors.forename: Mirko Moreno
authors.initials: MM
authors.lastname: Zaldivar
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
authors.forename: Tobias
authors.initials: T
authors.lastname: Mueller
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Ralf
authors.initials: R
authors.lastname: Weiskirchen
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.forename: Hermann E
authors.initials: HE
authors.lastname: Wasmuth
mesh_terms: D054392:Adipokines; D000328:Adult; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D006023:Glycoproteins / Q000097:blood* / Q000235:genetics* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications* / Q000235:genetics; D006801:Humans; D037102:Lectins; D008103:Liver Cirrhosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D012333:RNA, Messenger