Identification of an Endoglin Variant Associated With HCV-Related Liver Fibrosis Progression by Next-Generation Sequencing.

Details

Serval ID
serval:BIB_B0F934669617
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of an Endoglin Variant Associated With HCV-Related Liver Fibrosis Progression by Next-Generation Sequencing.
Journal
Frontiers in genetics
Author(s)
About F., Bibert S., Jouanguy E., Nalpas B., Lorenzo L., Rattina V., Zarhrate M., Hanein S., Munteanu M., Müllhaupt B., Semela D., Semmo N., Casanova J.L., Theodorou I., Sultanik P., Poynard T., Pol S., Bochud P.Y., Cobat A., Abel L.
Working group(s)
Swiss Hepatitis C Cohort Study Group, French ANRS HC EP 26 Genoscan Study Group
Contributor(s)
Negro F., Hadengue A., Kaiser L., Rubbia-Brandt L., Moradpour D., Cellerai C., Rickenbach M., Cerny A., Martinetti G., Dufour J.F., Gorgievski M., Spicher V.M., Heim M., Hirsch H., Helbling B., Regenass S., Malinverni R., Dollenmaier G., Cathomas G., Bousquet L., Ngo Y., Lebray P., Moussalli J., Benhamou Y., Thabut D., Vallet-Pichard A., Fontaine H., Mallet V., Sogni P., Trabut J.B., Bourlière M., Delfraissy J.F.
ISSN
1664-8021 (Print)
ISSN-L
1664-8021
Publication state
Published
Issued date
2019
Peer-reviewed
Oui
Volume
10
Pages
1024
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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.
Keywords
HCV-related liver fibrosis, TGF-beta, endoglin, exome sequencing, rare-variant association study
Pubmed
Web of science
Create date
30/11/2019 12:36
Last modification date
28/01/2020 6:26
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