Z Gastroenterol 2009; 47 - P148
DOI: 10.1055/s-0029-1241398

Exclusion of the functional FAS promoter polymorphism -670A>G as a relevant factor for the development of advanced fibrosis or cirrhosis in patients with chronic liver disease

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: Recently a polymorphism in the tumor necrosis factor receptor superfamily 6 (FAS) gene has been associated with susceptibility to autoimmune hepatitis (Hiraide et al. Am J Gastroenterol 2005;100:1322–9) and advanced fibrosis (Agarwal et al Tissue Antigens 2007;69:227–35). We aimed to verify this association in a cohort of patients with chronic liver diseases.

Patients and methods: Overall, we enrolled 790 patients with chronic liver diseases of mixed aetiologies, including a subset of 60 patients with autoimmune associated liver diseases (AIH, PBC and PBC). Liver fibrosis stages were determined by transient elastography (TE). In addition, we recruited patients with unequivocal signs of liver cirrhosis in whom TE could not be performed, e.g. because of 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 FAS SNP -670A>G using quantitative real-time PCR with fluorescent dye labelled probes.

Results: Fibrosis was not associated with the FAS -670A>G polymorphism in the overall cohort of patients with chronic liver diseases. In order to test for an association with advanced fibrosis and cirrhosis, we also stratified our patients in patients with cirrhosis and non-significant fibrosis (TE <7.5 kPa). However also in these phenotypically extreme groups, no association was detected. Finally, we did not detect an association in the subgroup of patients with autoimmune associated liver diseases such as AIH, PBC and PSC.

Conclusions: Liver fibrosis and cirrhosis are not associated with the -670A>G polymorphism of the FAS gene in our cohort. However, further studies are needed in order to replicate the initial findings and to exclude an effect on disease susceptibility in non-autoimmune chronic liver diseases such as HCV infection.