Z Gastroenterol 2009; 47 - P112
DOI: 10.1055/s-0029-1241363

A functional promoter polymorphism in the chitinase-like protein gene (CH3L1) is associated with liver fibrosis in a FibroScan staged cohort

F Grünhage 1, M Krawczyk 1, R Goebel 1, T Sauerbruch 2, F Lammert 1
  • 1Universitätsklinik des Saarlandes, Medizinische Klinik II, Homburg, Germany
  • 2Universitätsklinik Bonn, Medizinische Klinik I, Bonn, Germany

Introduction: Cartilage glycoprotein-39 (YKL-40) is supposed to be involved in tissue remodelling and degradation of extracellular matrix. Recently a functional promoter variant (-131G>C) of the corresponding gene CH3L1 has been associated with advanced liver fibrosis in patients with chronic hepatitis C virus (HCV) infection (Berres et al. J Hepatol 2009;50:370–376). We aimed to verify this association in a cohort of patients with mixed aetiologies of chronic liver disease and in a subgroup of patients with ongoing HCV infection.

Patients and methods: We enrolled 790 patients with chronic liver diseases, including a subset of 448 patients with chronic HCV infection. Liver fibrosis stage was determined by transient elastography (TE). In addition, we included patients with unequivocal signs of liver cirrhosis in whom TE could not be performed, e.g. due to ascites. We stratified patients in a fibrosis group (TE >7.5 kPa or signs of liver cirrhosis) and a no-fibrosis group (TE <7.5 kPa). Patients were genotyped for the CH3L1 SNPs described by Berres et al.

Results: Carriers for the rare allele of the -131G>C variant in the CH3L1 gene are at increased risk for liver fibrosis (OR=1.45, C.I.=[1.08–1.96]; p=0.014). In contrast to the initial study, this association could not be replicated in HCV patients. However in the complete cohort, the association proved to be robust in a regression analysis including carrier status of the rare CH3L1 allele as well as age and gender as covariates (OR=1.50, C.I.=[1.11–2.04]; p<0.001).

Conclusions: This study provides further evidence for an association of the previously reported promoter variant of the CH3L1 gene with liver fibrosis. However, our results show a more general association irrespective of the underlying aetiology. Furthermore, we demonstrate that fibrosis staging with TE is valid and may thus be employed in further genetic association studies in chronic liver disease.