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.
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 infectedpatients (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 infectedpatients (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: Marie-Luise Berres; Rory R Koenen; Anna Rueland; Mirko Moreno Zaldivar; Daniel Heinrichs; Hacer Sahin; Petra Schmitz; Konrad L Streetz; Thomas Berg; Nikolaus Gassler; Ralf Weiskirchen; Amanda Proudfoot; Christian Weber; Christian Trautwein; Hermann E Wasmuth Journal: J Clin Invest Date: 2010-10-18 Impact factor: 14.808
Authors: Amal Ahmed Abd El-Fattah; Nermin Abdel Hamid Sadik; Olfat Gamil Shaker; Amal Mohamed Kamal Journal: Mediators Inflamm Date: 2018-10-25 Impact factor: 4.711
Authors: Robert J Fontana; Jules L Dienstag; Herbert L Bonkovsky; Richard K Sterling; Deepa Naishadham; Zachary D Goodman; Anna S F Lok; Elizabeth C Wright; Grace L Su Journal: Gut Date: 2010-07-30 Impact factor: 23.059
Authors: Robert J Fontana; Heather J Litman; Jules L Dienstag; Herbert L Bonkovsky; Grace Su; Richard K Sterling; Anna S Lok Journal: Liver Int Date: 2011-11-22 Impact factor: 5.828