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An AGTR1 Variant Worsens Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome

de Gracia Hahn, Dana, BA1; Duret, Amedine, BA1; Mann, Jake P., MRCP, MRCPCH2,3

American Journal of Gastroenterology: April 2019 - Volume 114 - Issue 4 - p 556–559
doi: 10.14309/ajg.0000000000000193
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Nonalcoholic fatty liver disease and hypertension are closely related but there has been little genetic evidence to link them. In this issue, Musso et al. provide evidence that a common variant in AGTR1 (A1166C) is associated with both incident hypertension and nonalcoholic fatty liver disease, as well as nonalcoholic steatohepatitis, fibrosis, dyslipidemia, and insulin resistance. AGTR1 is strongly expressed in adipose, liver, and arteries. The mechanism of this gain-of-function variant is unclear but may include adipose or endothelial dysfunction and immune activation. Despite previous unsuccessful clinical trials of angiotensin receptor blockers in nonalcoholic steatohepatitis, individuals with the rs5186A>C variant may have greater benefit from this therapy.

1School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom;

2Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom;

3Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom.

Correspondence: Jake P. Mann, MRCP, MRCPCH. E-mail: jm2032@cam.ac.uk.

Received January 04, 2019

Accepted February 11, 2019

© The American College of Gastroenterology 2019. All Rights Reserved.
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