دورية أكاديمية
High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis
| العنوان: | High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis |
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| المؤلفون: | Schmalz, Franziska, Fischer, Janett, Innes, Hamish, Buch, Stephan, Moller, Christine, Matz-Soja, Madlen, von Schonfels, Witigo, Kramer, Benjamin, Langhans, Bettina, Kluners, Alexandra, Soyka, Michael, Stickel, Felix, Nattermann, Jacob, Strassburg, Christian P., Berg, Thomas, Lutz, Philipp, Nischalke, Hans Dieter |
| المصدر: | Schmalz , F , Fischer , J , Innes , H , Buch , S , Moller , C , Matz-Soja , M , von Schonfels , W , Kramer , B , Langhans , B , Kluners , A , Soyka , M , Stickel , F , Nattermann , J , Strassburg , C P , Berg , T , Lutz , P & Nischalke , H D 2023 , ' High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis ' , JHEP Reports , vol. 5 , no. 4 , 100684 .... |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cirrhosis, Alcohol-associated liver disease, HCC, LPL, rs13702, rs328, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, name=SDG 3 - Good Health and Well-being, /dk/atira/pure/subjectarea/asjc/2700/2715, name=Gastroenterology, /dk/atira/pure/subjectarea/asjc/2700/2724, name=Internal Medicine, /dk/atira/pure/subjectarea/asjc/2700/2723, name=Immunology and Allergy, /dk/atira/pure/subjectarea/asjc/2700/2721, name=Hepatology |
| الوصف: | 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://researchonline.gcu.ac.uk/en/publications/53273a0b-f42a-45da-b565-664cb6690f14Test |
| DOI: | 10.1016/j.jhepr.2023.100684 |
| الإتاحة: | https://doi.org/10.1016/j.jhepr.2023.100684Test https://researchonline.gcu.ac.uk/en/publications/53273a0b-f42a-45da-b565-664cb6690f14Test https://researchonline.gcu.ac.uk/ws/files/69398673/PIIS2589555923000150.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7B530FF8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jhepr.2023.100684 |
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