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HSD17B13 truncated variant is associated with a mild hepatic phenotype in Wilson’s Disease

HSD17B13 encodes hydroxysteroid 17-β dehydrogenase 13, a novel liver lipid-droplet associated protein that is involved in the regulation of lipid biosynthetic processes. A protein-truncating HSD17B13 variant (rs72613567) was shown to protect individuals from alcoholic and non-alcoholic liver disease...

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Autores principales: Ferenci, Peter, Pfeiffenberger, Jan, Stättermayer, Albert Friedrich, Stauber, Rudolf E., Willheim, Claudia, Weiss, Karl H., Munda-Steindl, Petra, Trauner, Michael, Schilsky, Michael, Zoller, Heinz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001574/
https://www.ncbi.nlm.nih.gov/pubmed/32039348
http://dx.doi.org/10.1016/j.jhepr.2019.02.007
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author Ferenci, Peter
Pfeiffenberger, Jan
Stättermayer, Albert Friedrich
Stauber, Rudolf E.
Willheim, Claudia
Weiss, Karl H.
Munda-Steindl, Petra
Trauner, Michael
Schilsky, Michael
Zoller, Heinz
author_facet Ferenci, Peter
Pfeiffenberger, Jan
Stättermayer, Albert Friedrich
Stauber, Rudolf E.
Willheim, Claudia
Weiss, Karl H.
Munda-Steindl, Petra
Trauner, Michael
Schilsky, Michael
Zoller, Heinz
author_sort Ferenci, Peter
collection PubMed
description HSD17B13 encodes hydroxysteroid 17-β dehydrogenase 13, a novel liver lipid-droplet associated protein that is involved in the regulation of lipid biosynthetic processes. A protein-truncating HSD17B13 variant (rs72613567) was shown to protect individuals from alcoholic and non-alcoholic liver disease. Since steatosis is a common feature in Wilson’s disease (WD), we aimed to assess whether the HSD17B13 variant modulates the phenotypic presentation and progression of WD. METHODS: The HSD17B13:TA (rs72613567) variant was determined by allelic discrimination real-time PCR in 586 patients. The HSD17B13 genotype was correlated with the phenotypic presentation. The age of onset and the type of symptoms at presentation were used as markers of the WD phenotype. RESULTS: The overall HSD17B13:TA allele frequency in patients with WD was 23.3% (273/1,172), not significantly different from the reported minor allele frequency. There was a significantly lower HSD17B13:TA allele frequency in patients with fulminant WD compared to all other phenotypic WD groups (11.0% vs. 24.0%, p < 0.01). Among the patients with fulminant WD there was a trend for a gender effect; none of the male patients carried the HSD17B13:TA allele. HSD17B13:TA allele frequency was more common in patients with minimal or no fibrosis (49 [31.1%] had simple steatosis and 20 minimal changes at biopsy) than in patients with cirrhosis or advanced fibrosis (22.3%, p = 0.025). CONCLUSIONS: The HSD17B13:TA allele modulates the phenotype and outcome of WD. This allele likely ameliorates hepatic fibrosis and reduces the transition from copper induced hemolysis to fulminant disease in patients with WD. LAY SUMMARY: Wilson‘s disease is a hereditary disease caused by accumulation of copper in the liver and other tissues. It presents with a variety of clinical symptoms. In this study we explored the role of a recently described gene mutation (HSD17B13:TA) which apparently protects the liver against toxins like alcohol. The results indicate that this mutation plays a role in the evolution of liver disease. Patients with Wilson's disease who carry this mutation are more likely to have mild disease, while the absence of the mutation is associated with the most severe form – fulminant Wilson’s disease.
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spelling pubmed-70015742020-02-07 HSD17B13 truncated variant is associated with a mild hepatic phenotype in Wilson’s Disease Ferenci, Peter Pfeiffenberger, Jan Stättermayer, Albert Friedrich Stauber, Rudolf E. Willheim, Claudia Weiss, Karl H. Munda-Steindl, Petra Trauner, Michael Schilsky, Michael Zoller, Heinz JHEP Rep Research Article HSD17B13 encodes hydroxysteroid 17-β dehydrogenase 13, a novel liver lipid-droplet associated protein that is involved in the regulation of lipid biosynthetic processes. A protein-truncating HSD17B13 variant (rs72613567) was shown to protect individuals from alcoholic and non-alcoholic liver disease. Since steatosis is a common feature in Wilson’s disease (WD), we aimed to assess whether the HSD17B13 variant modulates the phenotypic presentation and progression of WD. METHODS: The HSD17B13:TA (rs72613567) variant was determined by allelic discrimination real-time PCR in 586 patients. The HSD17B13 genotype was correlated with the phenotypic presentation. The age of onset and the type of symptoms at presentation were used as markers of the WD phenotype. RESULTS: The overall HSD17B13:TA allele frequency in patients with WD was 23.3% (273/1,172), not significantly different from the reported minor allele frequency. There was a significantly lower HSD17B13:TA allele frequency in patients with fulminant WD compared to all other phenotypic WD groups (11.0% vs. 24.0%, p < 0.01). Among the patients with fulminant WD there was a trend for a gender effect; none of the male patients carried the HSD17B13:TA allele. HSD17B13:TA allele frequency was more common in patients with minimal or no fibrosis (49 [31.1%] had simple steatosis and 20 minimal changes at biopsy) than in patients with cirrhosis or advanced fibrosis (22.3%, p = 0.025). CONCLUSIONS: The HSD17B13:TA allele modulates the phenotype and outcome of WD. This allele likely ameliorates hepatic fibrosis and reduces the transition from copper induced hemolysis to fulminant disease in patients with WD. LAY SUMMARY: Wilson‘s disease is a hereditary disease caused by accumulation of copper in the liver and other tissues. It presents with a variety of clinical symptoms. In this study we explored the role of a recently described gene mutation (HSD17B13:TA) which apparently protects the liver against toxins like alcohol. The results indicate that this mutation plays a role in the evolution of liver disease. Patients with Wilson's disease who carry this mutation are more likely to have mild disease, while the absence of the mutation is associated with the most severe form – fulminant Wilson’s disease. Elsevier 2019-03-19 /pmc/articles/PMC7001574/ /pubmed/32039348 http://dx.doi.org/10.1016/j.jhepr.2019.02.007 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Ferenci, Peter
Pfeiffenberger, Jan
Stättermayer, Albert Friedrich
Stauber, Rudolf E.
Willheim, Claudia
Weiss, Karl H.
Munda-Steindl, Petra
Trauner, Michael
Schilsky, Michael
Zoller, Heinz
HSD17B13 truncated variant is associated with a mild hepatic phenotype in Wilson’s Disease
title HSD17B13 truncated variant is associated with a mild hepatic phenotype in Wilson’s Disease
title_full HSD17B13 truncated variant is associated with a mild hepatic phenotype in Wilson’s Disease
title_fullStr HSD17B13 truncated variant is associated with a mild hepatic phenotype in Wilson’s Disease
title_full_unstemmed HSD17B13 truncated variant is associated with a mild hepatic phenotype in Wilson’s Disease
title_short HSD17B13 truncated variant is associated with a mild hepatic phenotype in Wilson’s Disease
title_sort hsd17b13 truncated variant is associated with a mild hepatic phenotype in wilson’s disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001574/
https://www.ncbi.nlm.nih.gov/pubmed/32039348
http://dx.doi.org/10.1016/j.jhepr.2019.02.007
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