A functional variation in CHI3L1 is associated with severity of liver fibrosis and YKL-40 serum levels in chronic hepatitis C infection.
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.
Berres
Marie-Luise
ML
Department of Internal Medicine III, University Hospital Aachen, RWTH Aachen, Pauwelsstr. 30, D-52057 Aachen, Germany.
Papen
Sven
S
Pauels
Katrin
K
Schmitz
Petra
P
Zaldivar
Mirko Moreno
MM
Hellerbrand
Claus
C
Mueller
Tobias
T
Berg
Thomas
T
Weiskirchen
Ralf
R
Trautwein
Christian
C
Wasmuth
Hermann E
HE
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
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D012333:RNA, Messenger