MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

Khaled Thabet; Anastasia Asimakopoulos; Maryam Shojaei; Manuel Romero-Gomez; Alessandra Mangia; William L. Irving; Thomas Berg; Gregory J. Dore; Henning Grønbæk; David Sheridan; Maria Lorena Abate; Elisabetta Bugianesi; Martin Weltman; Lindsay Mollison; Wendy Cheng; Stephen Riordan; Janett Fischer; Ulrich Spengler; Jacob Nattermann; Ahmed Wahid; Angela Rojas; Rose White; Mark W. Douglas; Duncan McLeod; Elizabeth Powell; Christopher Liddle; David Van Der Poorten; Jacob George; Mohammed Eslam; Rocio Gallego-Duran; Tanya Applegate; Margaret Bassendine; Chiara Rosso; Lavinia Mezzabotta; Reynold Leung; Barbara Malik; Gail Matthews; Jason Grebely; Vincenzo Fragomeli; Julie R. Jonsson; Rosanna Santoro

doi:10.1038/ncomms12757

MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

Khaled Thabet, Anastasia Asimakopoulos, Maryam Shojaei, Manuel Romero-Gomez, Alessandra Mangia, William L. Irving, Thomas Berg, Gregory J. Dore, Henning Grønbæk, David Sheridan, Maria Lorena Abate, Elisabetta Bugianesi, Martin Weltman, Lindsay Mollison, Wendy Cheng, Stephen Riordan, Janett Fischer, Ulrich Spengler, Jacob Nattermann, Ahmed WahidAngela Rojas, Rose White, Mark W. Douglas, Duncan McLeod, Elizabeth Powell, Christopher Liddle, David Van Der Poorten, Jacob George, Mohammed Eslam, Rocio Gallego-Duran, Tanya Applegate, Margaret Bassendine, Chiara Rosso, Lavinia Mezzabotta, Reynold Leung, Barbara Malik, Gail Matthews, Jason Grebely, Vincenzo Fragomeli, Julie R. Jonsson, Rosanna Santoro

IRCCS Casa Sollievo della Sofferenza

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Abstract

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.

Original language	English
Article number	12757
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12757
Publication status	Published - Sep 15 2016

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Thabet, K., Asimakopoulos, A., Shojaei, M., Romero-Gomez, M., Mangia, A., Irving, W. L., Berg, T., Dore, G. J., Grønbæk, H., Sheridan, D., Abate, M. L., Bugianesi, E., Weltman, M., Mollison, L., Cheng, W., Riordan, S., Fischer, J., Spengler, U., Nattermann, J., ... Santoro, R. (2016). MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C. Nature Communications, 7, [12757]. https://doi.org/10.1038/ncomms12757

Thabet, K, Asimakopoulos, A, Shojaei, M, Romero-Gomez, M, Mangia, A, Irving, WL, Berg, T, Dore, GJ, Grønbæk, H, Sheridan, D, Abate, ML, Bugianesi, E, Weltman, M, Mollison, L, Cheng, W, Riordan, S, Fischer, J, Spengler, U, Nattermann, J, Wahid, A, Rojas, A, White, R, Douglas, MW, McLeod, D, Powell, E, Liddle, C, Van Der Poorten, D, George, J, Eslam, M, Gallego-Duran, R, Applegate, T, Bassendine, M, Rosso, C, Mezzabotta, L, Leung, R, Malik, B, Matthews, G, Grebely, J, Fragomeli, V, Jonsson, JR & Santoro, R 2016, 'MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C', Nature Communications, vol. 7, 12757. https://doi.org/10.1038/ncomms12757

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title = "MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C",

abstract = "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.",

author = "Khaled Thabet and Anastasia Asimakopoulos and Maryam Shojaei and Manuel Romero-Gomez and Alessandra Mangia and Irving, {William L.} and Thomas Berg and Dore, {Gregory J.} and Henning Gr{\o}nb{\ae}k and David Sheridan and Abate, {Maria Lorena} and Elisabetta Bugianesi and Martin Weltman and Lindsay Mollison and Wendy Cheng and Stephen Riordan and Janett Fischer and Ulrich Spengler and Jacob Nattermann and Ahmed Wahid and Angela Rojas and Rose White and Douglas, {Mark W.} and Duncan McLeod and Elizabeth Powell and Christopher Liddle and {Van Der Poorten}, David and Jacob George and Mohammed Eslam and Rocio Gallego-Duran and Tanya Applegate and Margaret Bassendine and Chiara Rosso and Lavinia Mezzabotta and Reynold Leung and Barbara Malik and Gail Matthews and Jason Grebely and Vincenzo Fragomeli and Jonsson, {Julie R.} and Rosanna Santoro",

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doi = "10.1038/ncomms12757",

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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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ER -

MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

Abstract

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