A genetic variant in toll-like receptor 5 is linked to chemokine levels and hepatocellular carcinoma in steatohepatitis
© 2021 The Authors. Liver International published by John Wiley & Sons Ltd..
BACKGROUND & AIMS: Bacterial translocation drives liver disease progression. We investigated whether functional genetic variants in toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, affect the risk for hepatocellular carcinoma (HCC).
METHODS: Healthy controls (n = 212), patients with alcohol abuse without liver disease (n = 382), and patients from a discovery cohort of alcohol-associated cirrhosis (n = 372 including 79 HCC cases), a validation cohort of alcohol-associated cirrhosis (n = 355 including 132 HCC cases), and a cohort of cirrhosis due to nonalcoholic steatohepatitis (NASH) (n = 145 including 62 HCC cases) were genotyped for the TLR5 rs5744174 and rs5744168 polymorphisms. Chemokine levels were measured by ELISA in patients' sera and supernatants of flagellin-stimulated healthy monocytes.
RESULTS: Frequency of the TLR5 rs5744174 TT genotype was similar in healthy controls (33%), controls with alcohol abuse (34%), and patients with alcohol-associated cirrhosis in the discovery (28%), validation (33%), and NASH cohort (31%). The TT genotype was enriched in patients with versus without HCC in the discovery, validation, and NASH cohort (41% vs 25%; 39% vs 29%; 40% vs 24%; p < .05 each). This genotype remained a risk factor for HCC (OR = 1.9; p = .01) after multivariate correction for age, gender, diabetes, and carriage of the PNPLA3 148M variant. Interleukin-8 induction in monocytes from healthy controls and serum levels of interleukin-8 and CXCL1 from cirrhotic patients with the TT genotype were significantly increased versus C allele carriers.
CONCLUSION: The TLR5 rs5744174 polymorphism, affecting immune response to flagellin, is linked to occurrence of HCC in cirrhosis caused by steatohepatitis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
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| Enthalten in: |
Liver international : official journal of the International Association for the Study of the Liver - 41(2021), 9 vom: 23. Sept., Seite 2139-2148 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nischalke, Hans Dieter [VerfasserIn] |
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| Links: |
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| Themen: |
Alcoholic liver disease |
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| Anmerkungen: |
Date Completed 19.08.2021 Date Revised 31.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/liv.14980 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM32599725X |
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| 100 | 1 | |a Nischalke, Hans Dieter |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A genetic variant in toll-like receptor 5 is linked to chemokine levels and hepatocellular carcinoma in steatohepatitis |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 19.08.2021 | ||
| 500 | |a Date Revised 31.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. Liver International published by John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND & AIMS: Bacterial translocation drives liver disease progression. We investigated whether functional genetic variants in toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, affect the risk for hepatocellular carcinoma (HCC) | ||
| 520 | |a METHODS: Healthy controls (n = 212), patients with alcohol abuse without liver disease (n = 382), and patients from a discovery cohort of alcohol-associated cirrhosis (n = 372 including 79 HCC cases), a validation cohort of alcohol-associated cirrhosis (n = 355 including 132 HCC cases), and a cohort of cirrhosis due to nonalcoholic steatohepatitis (NASH) (n = 145 including 62 HCC cases) were genotyped for the TLR5 rs5744174 and rs5744168 polymorphisms. Chemokine levels were measured by ELISA in patients' sera and supernatants of flagellin-stimulated healthy monocytes | ||
| 520 | |a RESULTS: Frequency of the TLR5 rs5744174 TT genotype was similar in healthy controls (33%), controls with alcohol abuse (34%), and patients with alcohol-associated cirrhosis in the discovery (28%), validation (33%), and NASH cohort (31%). The TT genotype was enriched in patients with versus without HCC in the discovery, validation, and NASH cohort (41% vs 25%; 39% vs 29%; 40% vs 24%; p < .05 each). This genotype remained a risk factor for HCC (OR = 1.9; p = .01) after multivariate correction for age, gender, diabetes, and carriage of the PNPLA3 148M variant. Interleukin-8 induction in monocytes from healthy controls and serum levels of interleukin-8 and CXCL1 from cirrhotic patients with the TT genotype were significantly increased versus C allele carriers | ||
| 520 | |a CONCLUSION: The TLR5 rs5744174 polymorphism, affecting immune response to flagellin, is linked to occurrence of HCC in cirrhosis caused by steatohepatitis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a IL-8 | |
| 650 | 4 | |a NAFLD | |
| 650 | 4 | |a alcoholic liver disease | |
| 650 | 4 | |a cirrhosis | |
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| 650 | 7 | |a Toll-Like Receptor 5 |2 NLM | |
| 700 | 1 | |a Fischer, Janett |e verfasserin |4 aut | |
| 700 | 1 | |a Klüners, Alexandra |e verfasserin |4 aut | |
| 700 | 1 | |a Matz-Soja, Madlen |e verfasserin |4 aut | |
| 700 | 1 | |a Krämer, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Langhans, Bettina |e verfasserin |4 aut | |
| 700 | 1 | |a Goeser, Felix |e verfasserin |4 aut | |
| 700 | 1 | |a Soyka, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Stickel, Felix |e verfasserin |4 aut | |
| 700 | 1 | |a Spengler, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Nattermann, Jacob |e verfasserin |4 aut | |
| 700 | 1 | |a Strassburg, Christian P |e verfasserin |4 aut | |
| 700 | 1 | |a Berg, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Lutz, Philipp |e verfasserin |4 aut | |
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