Publikation
Identification of an Endoglin Variant Associated With HCV-Related Liver Fibrosis Progression by Next-Generation Sequencing
Wissenschaftlicher Artikel/Review - 04.11.2019
About Frédégonde, Casanova Jean-Laurent, Theodorou Ioannis, Sultanik Philippe, Poynard Thierry, Pol Stanislas, Bochud Pierre-Yves, Cobat Aurélie, Abel Laurent, Swiss Hepatitis C Cohort Study Group, Semmo Nasser, Semela David, Bibert Stéphanie, Jouanguy Emmanuelle, Nalpas Bertrand, Lorenzo Lazaro, Rattina Vimel, Zarhrate Mohammed, Hanein Sylvain, Munteanu Mona, Mullhaupt Beat, French ANRS HC EP 26 Genoscan Study Group
Bereiche
PubMed
DOI
Zitation
Art
Zeitschrift
Veröffentlichungsdatum
ISSN (Druck)
Seiten
Kurzbeschreibung/Zielsetzung
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 () in fibrosis patients. Replication studies in additional cohorts (617 patients) identified one specific 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.