TY - JOUR
T1 - MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C
AU - Thabet, Khaled
AU - Asimakopoulos, Anastasia
AU - Shojaei, Maryam
AU - Romero-Gomez, Manuel
AU - Mangia, Alessandra
AU - Irving, William L.
AU - Berg, Thomas
AU - Dore, Gregory J.
AU - Grønbæk, Henning
AU - Sheridan, David
AU - Abate, Maria Lorena
AU - Bugianesi, Elisabetta
AU - Weltman, Martin
AU - Mollison, Lindsay
AU - Cheng, Wendy
AU - Riordan, Stephen
AU - Fischer, Janett
AU - Spengler, Ulrich
AU - Nattermann, Jacob
AU - Wahid, Ahmed
AU - Rojas, Angela
AU - White, Rose
AU - Douglas, Mark W.
AU - McLeod, Duncan
AU - Powell, Elizabeth
AU - Liddle, Christopher
AU - Van Der Poorten, David
AU - George, Jacob
AU - Eslam, Mohammed
AU - Gallego-Duran, Rocio
AU - Applegate, Tanya
AU - Bassendine, Margaret
AU - Rosso, Chiara
AU - Mezzabotta, Lavinia
AU - Leung, Reynold
AU - Malik, Barbara
AU - Matthews, Gail
AU - Grebely, Jason
AU - Fragomeli, Vincenzo
AU - Jonsson, Julie R.
AU - Santoro, Rosanna
PY - 2016/9/15
Y1 - 2016/9/15
N2 - Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis.
AB - Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis.
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UR - http://www.scopus.com/inward/citedby.url?scp=84987829315&partnerID=8YFLogxK
U2 - 10.1038/ncomms12757
DO - 10.1038/ncomms12757
M3 - Article
AN - SCOPUS:84987829315
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 12757
ER -