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

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. [Copyright &y& Elsevier]