RT Journal Article
T1 Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes.
A1 Eslam, Mohammed
A1 Mangia, Alessandra
A1 Berg, Thomas
A1 Chan, Henry Lik Yuen
A1 Irving, William L
A1 Dore, Gregory J
A1 Abate, Maria Lorena
A1 Bugianesi, Elisabetta
A1 Adams, Leon A
A1 Najim, Mustafa A M
A1 Miele, Luca
A1 Weltman, Martin
A1 Mollison, Lindsay
A1 Cheng, Wendy
A1 Riordan, Stephen
A1 Fischer, Janett
A1 Romero-Gomez, Manuel
A1 Spengler, Ulrich
A1 Nattermann, Jacob
A1 Rahme, Antony
A1 Sheridan, David
A1 Booth, David R
A1 McLeod, Duncan
A1 Powell, Elizabeth
A1 Liddle, Christopher
A1 Douglas, Mark W
A1 van der Poorten, David
A1 George, Jacob
A1 International Liver Disease Genetics Consortium, 
AB A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The roles of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD and viral load in chronic viral hepatitis, as well as its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3260 subjects with viral and nonviral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of TM6SF2 and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls (P = 0.02) but not different in cohorts with CHC (n = 2023) and chronic hepatitis B (n = 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases and with reduced hepatic TM6SF2 and microsomal triglyceride transfer protein expression. Interestingly, the substitution was associated with reduced CHC viral load but increased hepatitis B virus DNA. The rs58542926 T allele had no effect on inflammation, impacted ≥F2 fibrosis in CHC and NAFLD assessed cross-sectionally (odds ratio = 1.39, 95% confidence interval 1.04-1.87, and odds ratio = 1.62, 95% confidence interval 1.03-2.52, respectively; P  The TM6SF2 E167K substitution promotes steatosis and lipid abnormalities in part by altering TM6SF2 and microsomal triglyceride transfer protein expression and differentially impacts CHC and chronic hepatitis B viral load, while effects on fibrosis are marginal. (Hepatology 2016;64:34-46).
YR 2016
FD 2016-03-30
LK http://hdl.handle.net/10668/9788
UL http://hdl.handle.net/10668/9788
LA en
DS RISalud
RD Apr 7, 2025