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Göteborgs universitets publikationer

DEPDC5 variants increase fibrosis progression in Europeans with chronic HCV infection.

Författare och institution:
Maria Antonella Burza (-); Benedetta Maria Motta (-); Rosellina Margherita Mancina (-); Piero Pingitore (-); Carlo Pirazzi (-); Saverio Massimo Lepore (-); Rocco Spagnuolo (-); Patrizia Doldo (-); Cristina Russo (-); Veronica Lazzaro (-); Janett Fischer (-); Thomas Berg (-); Alessio Aghemo (-); Cristina Cheroni (-); Raffaele De Francesco (-); Silvia Fargion (-); Massimo Colombo (-); Christian Datz (-); Felix Stickel (-); Luca Valenti (-); Stefano Romeo (Institutionen för medicin, avdelningen för molekylär och klinisk medicin)
Publicerad i:
Hepatology (Baltimore, Md.), 63 ( 2 ) s. 418-427
ISSN:
1527-3350
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2016
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
Chronic hepatitis C virus (HCV) infection may progress to cirrhosis and hepatocellular carcinoma (HCC). Recently, two genetic variants, DEPDC5 rs1012068 and MICA rs2596542, were associated with the onset of HCC in Asian subjects with chronic HCV infection. The aim of the present study was to analyze whether DEPDC5 and MICA genetic variants were associated with liver disease progression in Europeans with chronic HCV infection. In a Northern Italian discovery cohort (n=477), neither DEPDC5 rs1012068 nor MICA rs2596542 were associated with HCC (n=150). However, DEPDC5 rs1012068 was independently associated with cirrhosis (n=300; p=0.049). The association of rs1012068 with moderate-severe fibrosis was confirmed in an independent cross-sectional German cohort (n=415; p=0.006). Furthermore, DEPDC5 rs1012068 predicted faster fibrosis progression in a prospective cohort (n=247; p=0.027). Next, we examined the distribution of non-synonymous DEPDC5 variants in the overall cross-sectional cohort (n=912). The presence of at least one variant increased the risk of moderate/severe fibrosis by 54% (p=0.040). To understand the molecular mechanism underlying the genetic association of DEPDC5 variants with fibrosis progression, we performed in vitro studies on immortalized hepatic stellate cells (LX-2). In these cells, down-regulation of DEPDC5 resulted in increased expression of β-catenin and production of its target matrix metallopeptidase 2 (MMP2), a secreted enzyme involved in fibrosis progression.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Gastroenterologi
Nyckelord:
HCV DEPDC5
Postens nummer:
227264
Posten skapad:
2015-12-04 14:39
Posten ändrad:
2016-04-29 14:54

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