CONICET | Buscador de Institutos y Recursos Humanos

ABSTRACTCholestatic liver diseases encompass a complex spectrum of intrahepatic and cholangiocellular cholestasis, whoseetiologies include genetic and environmental components. This review focuses on the role of the genetic component of threeadult cholestatic diseases, namely, primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), and intrahepaticcholestasis of pregnancy (ICP). In particular, we integrate genomic, molecular, and physiological data to understand the putativeinterplay between the underlying genetic mechanisms involved in the susceptibility of these diseases. This approach is based onthe hypothesis that a more integrative knowledge of the genetic determinants of cholestatic diseases may have a strong impact onthe development of improved therapies. We also propose the strategy of gene prioritization to identity potential candidate genesfor disease susceptibility, and show some examples of leading genes of human cholestatic pathways. Finally, based on thehypothesis that common physiologic processes and molecular networks may influence the risk of adult cholestatic diseases, weused a candidate gene prioritization application based on the use of a proteinprotein interaction network as part of theinteractome.