AUTHOR=About Frédégonde , Bibert Stéphanie , Jouanguy Emmanuelle , Nalpas Bertrand , Lorenzo Lazaro , Rattina Vimel , Zarhrate Mohammed , Hanein Sylvain , Munteanu Mona , Müllhaupt Beat , Semela David , Semmo Nasser , Casanova Jean-Laurent , Theodorou Ioannis , Sultanik Philippe , Poynard Thierry , Pol Stanislas , Bochud Pierre-Yves , Cobat Aurélie , Abel Laurent , The Swiss Hepatitis C Cohort Study Group , The French ANRS HC EP 26 Genoscan Study Group , Negro Francesco , Hadengue Antoine , Kaiser Laurent , Rubbia-Brandt Laura , Moradpour Darius , Cellerai Cristina , Rickenbach Martin , Cerny Andreas , Martinetti Gladys , Dufour Jean-François , Gorgievski Meri , Spicher Virginie Masserey , Heim Markus , Hirsch Hans , Helbling Beat , Regenass Stephan , Malinverni Raffaele , Dollenmaier Guenter , Cathomas Gieri , Bousquet Laurence , Ngo Yen , Lebray Pascal , Moussalli Joseph , Benhamou Yves , Thabut Dominique , Vallet-Pichard Anaïs , Fontaine Hélène , Mallet Vincent , Sogni Philippe , Trabut Jean-Baptiste , Bourlière Marc , Delfraissy Jean-François TITLE=Identification of an Endoglin Variant Associated With HCV-Related Liver Fibrosis Progression by Next-Generation Sequencing JOURNAL=Frontiers in Genetics VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01024 DOI=10.3389/fgene.2019.01024 ISSN=1664-8021 ABSTRACT=

Despite the astonishing progress in treating chronic hepatitis C virus (HCV) infection with direct-acting antiviral agents, liver fibrosis remains a major health concern in HCV infected patients, in particular due to the treatment cost and insufficient HCV screening in many countries. Only a fraction of patients with chronic HCV infection develop liver fibrosis. While there is evidence that host genetic factors are involved in the development of liver fibrosis, the common variants identified so far, in particular by genome-wide association studies, were found to have limited effects. Here, we conducted an exome association study in 88 highly selected HCV-infected patients with and without fibrosis. A strategy focusing on TGF-β pathway genes revealed an enrichment in rare variants of the endoglin gene (ENG) in fibrosis patients. Replication studies in additional cohorts (617 patients) identified one specific ENG variant, Thr5Met, with an overall odds ratio for fibrosis development in carriers of 3.04 (1.39–6.69). Our results suggest that endoglin, a key player in TGF-β signaling, is involved in HCV-related liver fibrogenesis.