High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis

Background & Aims: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Franziska Schmalz [verfasserIn] Janett Fischer [verfasserIn] Hamish Innes [verfasserIn] Stephan Buch [verfasserIn] Christine Möller [verfasserIn] Madlen Matz-Soja [verfasserIn] Witigo von Schönfels [verfasserIn] Benjamin Krämer [verfasserIn] Bettina Langhans [verfasserIn] Alexandra Klüners [verfasserIn] Michael Soyka [verfasserIn] Felix Stickel [verfasserIn] Jacob Nattermann [verfasserIn] Christian P. Strassburg [verfasserIn] Thomas Berg [verfasserIn] Philipp Lutz [verfasserIn] Hans Dieter Nischalke [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Cirrhosis Alcohol-associated liver disease HCC LPL rs13702 rs328

Übergeordnetes Werk:	In: JHEP Reports - Elsevier, 2019, 5(2023), 4, Seite 100684-
Übergeordnetes Werk:	volume:5 ; year:2023 ; number:4 ; pages:100684-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.jhepr.2023.100684

Katalog-ID:	DOAJ079844189

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245	1	0	\|a High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis
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520			\|a Background & Aims: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis.
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650		4	\|a Alcohol-associated liver disease
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653		0	\|a Diseases of the digestive system. Gastroenterology
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700	0		\|a Hamish Innes \|e verfasserin \|4 aut
700	0		\|a Stephan Buch \|e verfasserin \|4 aut
700	0		\|a Christine Möller \|e verfasserin \|4 aut
700	0		\|a Madlen Matz-Soja \|e verfasserin \|4 aut
700	0		\|a Witigo von Schönfels \|e verfasserin \|4 aut
700	0		\|a Benjamin Krämer \|e verfasserin \|4 aut
700	0		\|a Bettina Langhans \|e verfasserin \|4 aut
700	0		\|a Alexandra Klüners \|e verfasserin \|4 aut
700	0		\|a Michael Soyka \|e verfasserin \|4 aut
700	0		\|a Felix Stickel \|e verfasserin \|4 aut
700	0		\|a Jacob Nattermann \|e verfasserin \|4 aut
700	0		\|a Christian P. Strassburg \|e verfasserin \|4 aut
700	0		\|a Thomas Berg \|e verfasserin \|4 aut
700	0		\|a Philipp Lutz \|e verfasserin \|4 aut
700	0		\|a Hans Dieter Nischalke \|e verfasserin \|4 aut
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author_variant	f s fs j f jf h i hi s b sb c m cm m m s mms w v s wvs b k bk b l bl a k ak m s ms f s fs j n jn c p s cps t b tb p l pl h d n hdn
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allfields	10.1016/j.jhepr.2023.100684 doi (DE-627)DOAJ079844189 (DE-599)DOAJ281715ab1def4e8eae95e524cbb821c1 DE-627 ger DE-627 rakwb eng RC799-869 Franziska Schmalz verfasserin aut High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background & Aims: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis. Cirrhosis Alcohol-associated liver disease HCC LPL rs13702 rs328 Diseases of the digestive system. Gastroenterology Janett Fischer verfasserin aut Hamish Innes verfasserin aut Stephan Buch verfasserin aut Christine Möller verfasserin aut Madlen Matz-Soja verfasserin aut Witigo von Schönfels verfasserin aut Benjamin Krämer verfasserin aut Bettina Langhans verfasserin aut Alexandra Klüners verfasserin aut Michael Soyka verfasserin aut Felix Stickel verfasserin aut Jacob Nattermann verfasserin aut Christian P. Strassburg verfasserin aut Thomas Berg verfasserin aut Philipp Lutz verfasserin aut Hans Dieter Nischalke verfasserin aut In JHEP Reports Elsevier, 2019 5(2023), 4, Seite 100684- (DE-627)166592800X 25895559 nnns volume:5 year:2023 number:4 pages:100684- https://doi.org/10.1016/j.jhepr.2023.100684 kostenfrei https://doaj.org/article/281715ab1def4e8eae95e524cbb821c1 kostenfrei http://www.sciencedirect.com/science/article/pii/S2589555923000150 kostenfrei https://doaj.org/toc/2589-5559 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 5 2023 4 100684-
spelling	10.1016/j.jhepr.2023.100684 doi (DE-627)DOAJ079844189 (DE-599)DOAJ281715ab1def4e8eae95e524cbb821c1 DE-627 ger DE-627 rakwb eng RC799-869 Franziska Schmalz verfasserin aut High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background & Aims: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis. Cirrhosis Alcohol-associated liver disease HCC LPL rs13702 rs328 Diseases of the digestive system. Gastroenterology Janett Fischer verfasserin aut Hamish Innes verfasserin aut Stephan Buch verfasserin aut Christine Möller verfasserin aut Madlen Matz-Soja verfasserin aut Witigo von Schönfels verfasserin aut Benjamin Krämer verfasserin aut Bettina Langhans verfasserin aut Alexandra Klüners verfasserin aut Michael Soyka verfasserin aut Felix Stickel verfasserin aut Jacob Nattermann verfasserin aut Christian P. Strassburg verfasserin aut Thomas Berg verfasserin aut Philipp Lutz verfasserin aut Hans Dieter Nischalke verfasserin aut In JHEP Reports Elsevier, 2019 5(2023), 4, Seite 100684- (DE-627)166592800X 25895559 nnns volume:5 year:2023 number:4 pages:100684- https://doi.org/10.1016/j.jhepr.2023.100684 kostenfrei https://doaj.org/article/281715ab1def4e8eae95e524cbb821c1 kostenfrei http://www.sciencedirect.com/science/article/pii/S2589555923000150 kostenfrei https://doaj.org/toc/2589-5559 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 5 2023 4 100684-
allfields_unstemmed	10.1016/j.jhepr.2023.100684 doi (DE-627)DOAJ079844189 (DE-599)DOAJ281715ab1def4e8eae95e524cbb821c1 DE-627 ger DE-627 rakwb eng RC799-869 Franziska Schmalz verfasserin aut High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background & Aims: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis. Cirrhosis Alcohol-associated liver disease HCC LPL rs13702 rs328 Diseases of the digestive system. Gastroenterology Janett Fischer verfasserin aut Hamish Innes verfasserin aut Stephan Buch verfasserin aut Christine Möller verfasserin aut Madlen Matz-Soja verfasserin aut Witigo von Schönfels verfasserin aut Benjamin Krämer verfasserin aut Bettina Langhans verfasserin aut Alexandra Klüners verfasserin aut Michael Soyka verfasserin aut Felix Stickel verfasserin aut Jacob Nattermann verfasserin aut Christian P. Strassburg verfasserin aut Thomas Berg verfasserin aut Philipp Lutz verfasserin aut Hans Dieter Nischalke verfasserin aut In JHEP Reports Elsevier, 2019 5(2023), 4, Seite 100684- (DE-627)166592800X 25895559 nnns volume:5 year:2023 number:4 pages:100684- https://doi.org/10.1016/j.jhepr.2023.100684 kostenfrei https://doaj.org/article/281715ab1def4e8eae95e524cbb821c1 kostenfrei http://www.sciencedirect.com/science/article/pii/S2589555923000150 kostenfrei https://doaj.org/toc/2589-5559 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 5 2023 4 100684-
allfieldsGer	10.1016/j.jhepr.2023.100684 doi (DE-627)DOAJ079844189 (DE-599)DOAJ281715ab1def4e8eae95e524cbb821c1 DE-627 ger DE-627 rakwb eng RC799-869 Franziska Schmalz verfasserin aut High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background & Aims: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis. Cirrhosis Alcohol-associated liver disease HCC LPL rs13702 rs328 Diseases of the digestive system. Gastroenterology Janett Fischer verfasserin aut Hamish Innes verfasserin aut Stephan Buch verfasserin aut Christine Möller verfasserin aut Madlen Matz-Soja verfasserin aut Witigo von Schönfels verfasserin aut Benjamin Krämer verfasserin aut Bettina Langhans verfasserin aut Alexandra Klüners verfasserin aut Michael Soyka verfasserin aut Felix Stickel verfasserin aut Jacob Nattermann verfasserin aut Christian P. Strassburg verfasserin aut Thomas Berg verfasserin aut Philipp Lutz verfasserin aut Hans Dieter Nischalke verfasserin aut In JHEP Reports Elsevier, 2019 5(2023), 4, Seite 100684- (DE-627)166592800X 25895559 nnns volume:5 year:2023 number:4 pages:100684- https://doi.org/10.1016/j.jhepr.2023.100684 kostenfrei https://doaj.org/article/281715ab1def4e8eae95e524cbb821c1 kostenfrei http://www.sciencedirect.com/science/article/pii/S2589555923000150 kostenfrei https://doaj.org/toc/2589-5559 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 5 2023 4 100684-
allfieldsSound	10.1016/j.jhepr.2023.100684 doi (DE-627)DOAJ079844189 (DE-599)DOAJ281715ab1def4e8eae95e524cbb821c1 DE-627 ger DE-627 rakwb eng RC799-869 Franziska Schmalz verfasserin aut High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background & Aims: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis. Cirrhosis Alcohol-associated liver disease HCC LPL rs13702 rs328 Diseases of the digestive system. Gastroenterology Janett Fischer verfasserin aut Hamish Innes verfasserin aut Stephan Buch verfasserin aut Christine Möller verfasserin aut Madlen Matz-Soja verfasserin aut Witigo von Schönfels verfasserin aut Benjamin Krämer verfasserin aut Bettina Langhans verfasserin aut Alexandra Klüners verfasserin aut Michael Soyka verfasserin aut Felix Stickel verfasserin aut Jacob Nattermann verfasserin aut Christian P. Strassburg verfasserin aut Thomas Berg verfasserin aut Philipp Lutz verfasserin aut Hans Dieter Nischalke verfasserin aut In JHEP Reports Elsevier, 2019 5(2023), 4, Seite 100684- (DE-627)166592800X 25895559 nnns volume:5 year:2023 number:4 pages:100684- https://doi.org/10.1016/j.jhepr.2023.100684 kostenfrei https://doaj.org/article/281715ab1def4e8eae95e524cbb821c1 kostenfrei http://www.sciencedirect.com/science/article/pii/S2589555923000150 kostenfrei https://doaj.org/toc/2589-5559 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 5 2023 4 100684-
language	English
source	In JHEP Reports 5(2023), 4, Seite 100684- volume:5 year:2023 number:4 pages:100684-
sourceStr	In JHEP Reports 5(2023), 4, Seite 100684- volume:5 year:2023 number:4 pages:100684-
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Cirrhosis Alcohol-associated liver disease HCC LPL rs13702 rs328 Diseases of the digestive system. Gastroenterology
isfreeaccess_bool	true
container_title	JHEP Reports
authorswithroles_txt_mv	Franziska Schmalz @@aut@@ Janett Fischer @@aut@@ Hamish Innes @@aut@@ Stephan Buch @@aut@@ Christine Möller @@aut@@ Madlen Matz-Soja @@aut@@ Witigo von Schönfels @@aut@@ Benjamin Krämer @@aut@@ Bettina Langhans @@aut@@ Alexandra Klüners @@aut@@ Michael Soyka @@aut@@ Felix Stickel @@aut@@ Jacob Nattermann @@aut@@ Christian P. Strassburg @@aut@@ Thomas Berg @@aut@@ Philipp Lutz @@aut@@ Hans Dieter Nischalke @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	166592800X
id	DOAJ079844189
language_de	englisch
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The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. 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callnumber-first	R - Medicine
author	Franziska Schmalz
spellingShingle	Franziska Schmalz misc RC799-869 misc Cirrhosis misc Alcohol-associated liver disease misc HCC misc LPL misc rs13702 misc rs328 misc Diseases of the digestive system. Gastroenterology High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis
authorStr	Franziska Schmalz
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topic_title	RC799-869 High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis Cirrhosis Alcohol-associated liver disease HCC LPL rs13702 rs328
topic	misc RC799-869 misc Cirrhosis misc Alcohol-associated liver disease misc HCC misc LPL misc rs13702 misc rs328 misc Diseases of the digestive system. Gastroenterology
topic_unstemmed	misc RC799-869 misc Cirrhosis misc Alcohol-associated liver disease misc HCC misc LPL misc rs13702 misc rs328 misc Diseases of the digestive system. Gastroenterology
topic_browse	misc RC799-869 misc Cirrhosis misc Alcohol-associated liver disease misc HCC misc LPL misc rs13702 misc rs328 misc Diseases of the digestive system. Gastroenterology
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title	High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis
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title_full	High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis
author_sort	Franziska Schmalz
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author_browse	Franziska Schmalz Janett Fischer Hamish Innes Stephan Buch Christine Möller Madlen Matz-Soja Witigo von Schönfels Benjamin Krämer Bettina Langhans Alexandra Klüners Michael Soyka Felix Stickel Jacob Nattermann Christian P. Strassburg Thomas Berg Philipp Lutz Hans Dieter Nischalke
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author-letter	Franziska Schmalz
doi_str_mv	10.1016/j.jhepr.2023.100684
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title_sort	high producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis
callnumber	RC799-869
title_auth	High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis
abstract	Background & Aims: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis.
abstractGer	Background & Aims: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis.
abstract_unstemmed	Background & Aims: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis.
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title_short	High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis
url	https://doi.org/10.1016/j.jhepr.2023.100684 https://doaj.org/article/281715ab1def4e8eae95e524cbb821c1 http://www.sciencedirect.com/science/article/pii/S2589555923000150 https://doaj.org/toc/2589-5559
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author2	Janett Fischer Hamish Innes Stephan Buch Christine Möller Madlen Matz-Soja Witigo von Schönfels Benjamin Krämer Bettina Langhans Alexandra Klüners Michael Soyka Felix Stickel Jacob Nattermann Christian P. Strassburg Thomas Berg Philipp Lutz Hans Dieter Nischalke
author2Str	Janett Fischer Hamish Innes Stephan Buch Christine Möller Madlen Matz-Soja Witigo von Schönfels Benjamin Krämer Bettina Langhans Alexandra Klüners Michael Soyka Felix Stickel Jacob Nattermann Christian P. Strassburg Thomas Berg Philipp Lutz Hans Dieter Nischalke
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doi_str	10.1016/j.jhepr.2023.100684
callnumber-a	RC799-869
up_date	2024-07-04T01:03:00.726Z
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The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. Methods: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. Results: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. Conclusions: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. Impact and implications: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cirrhosis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Alcohol-associated liver disease</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">HCC</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">LPL</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">rs13702</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">rs328</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Diseases of the digestive system. 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High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis

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