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The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis

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The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis. / Innes, Hamish; Nischalke, Hans Dieter; Guha, Indra Neil; Weiss, Karl Heinz; Irving, Will; Gotthardt, Daniel; Barnes, Eleanor; Fischer, Janett; Ansari, M Azim; Rosendahl, Jonas; Lin, Shang-Kuan; Marot, Astrid; Pedergnana, Vincent; Casper, Markus; Benselin, Jennifer; Lammert, Frank; McLauchlan, John; Lutz, Philip L; Hamill, Victoria; Mueller, Sebastian; Morling, Joanne R; Semmler, Georg; Eyer, Florian; von Felden, Johann; Link, Alexander; Vogel, Arndt; Marquardt, Jens U; Sulk, Stefan; Trebicka, Jonel; Valenti, Luca; Datz, Christian; Reiberger, Thomas; Schafmayer, Clemens; Berg, Thomas; Deltenre, Pierre; Hampe, Jochen; Stickel, Felix; Buch, Stephan.

in: HEPATOL COMMUN, Jahrgang 6, Nr. 5, 05.2022, S. 1213-1226.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Innes, H, Nischalke, HD, Guha, IN, Weiss, KH, Irving, W, Gotthardt, D, Barnes, E, Fischer, J, Ansari, MA, Rosendahl, J, Lin, S-K, Marot, A, Pedergnana, V, Casper, M, Benselin, J, Lammert, F, McLauchlan, J, Lutz, PL, Hamill, V, Mueller, S, Morling, JR, Semmler, G, Eyer, F, von Felden, J, Link, A, Vogel, A, Marquardt, JU, Sulk, S, Trebicka, J, Valenti, L, Datz, C, Reiberger, T, Schafmayer, C, Berg, T, Deltenre, P, Hampe, J, Stickel, F & Buch, S 2022, 'The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis', HEPATOL COMMUN, Jg. 6, Nr. 5, S. 1213-1226. https://doi.org/10.1002/hep4.1886

APA

Innes, H., Nischalke, H. D., Guha, I. N., Weiss, K. H., Irving, W., Gotthardt, D., Barnes, E., Fischer, J., Ansari, M. A., Rosendahl, J., Lin, S-K., Marot, A., Pedergnana, V., Casper, M., Benselin, J., Lammert, F., McLauchlan, J., Lutz, P. L., Hamill, V., ... Buch, S. (2022). The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis. HEPATOL COMMUN, 6(5), 1213-1226. https://doi.org/10.1002/hep4.1886

Vancouver

Innes H, Nischalke HD, Guha IN, Weiss KH, Irving W, Gotthardt D et al. The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis. HEPATOL COMMUN. 2022 Mai;6(5):1213-1226. https://doi.org/10.1002/hep4.1886

Bibtex

@article{3ebc0fca213b412a8231a4304dd89f7a,
title = "The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis",
abstract = "The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P = 2.9 × 10-5 ). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P = 3.1 × 10-6 ). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P = 0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.",
author = "Hamish Innes and Nischalke, {Hans Dieter} and Guha, {Indra Neil} and Weiss, {Karl Heinz} and Will Irving and Daniel Gotthardt and Eleanor Barnes and Janett Fischer and Ansari, {M Azim} and Jonas Rosendahl and Shang-Kuan Lin and Astrid Marot and Vincent Pedergnana and Markus Casper and Jennifer Benselin and Frank Lammert and John McLauchlan and Lutz, {Philip L} and Victoria Hamill and Sebastian Mueller and Morling, {Joanne R} and Georg Semmler and Florian Eyer and {von Felden}, Johann and Alexander Link and Arndt Vogel and Marquardt, {Jens U} and Stefan Sulk and Jonel Trebicka and Luca Valenti and Christian Datz and Thomas Reiberger and Clemens Schafmayer and Thomas Berg and Pierre Deltenre and Jochen Hampe and Felix Stickel and Stephan Buch",
note = "{\textcopyright} 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.",
year = "2022",
month = may,
doi = "10.1002/hep4.1886",
language = "English",
volume = "6",
pages = "1213--1226",
journal = "HEPATOL COMMUN",
issn = "2471-254X",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "5",

}

RIS

TY - JOUR

T1 - The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis

AU - Innes, Hamish

AU - Nischalke, Hans Dieter

AU - Guha, Indra Neil

AU - Weiss, Karl Heinz

AU - Irving, Will

AU - Gotthardt, Daniel

AU - Barnes, Eleanor

AU - Fischer, Janett

AU - Ansari, M Azim

AU - Rosendahl, Jonas

AU - Lin, Shang-Kuan

AU - Marot, Astrid

AU - Pedergnana, Vincent

AU - Casper, Markus

AU - Benselin, Jennifer

AU - Lammert, Frank

AU - McLauchlan, John

AU - Lutz, Philip L

AU - Hamill, Victoria

AU - Mueller, Sebastian

AU - Morling, Joanne R

AU - Semmler, Georg

AU - Eyer, Florian

AU - von Felden, Johann

AU - Link, Alexander

AU - Vogel, Arndt

AU - Marquardt, Jens U

AU - Sulk, Stefan

AU - Trebicka, Jonel

AU - Valenti, Luca

AU - Datz, Christian

AU - Reiberger, Thomas

AU - Schafmayer, Clemens

AU - Berg, Thomas

AU - Deltenre, Pierre

AU - Hampe, Jochen

AU - Stickel, Felix

AU - Buch, Stephan

N1 - © 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.

PY - 2022/5

Y1 - 2022/5

N2 - The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P = 2.9 × 10-5 ). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P = 3.1 × 10-6 ). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P = 0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.

AB - The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P = 2.9 × 10-5 ). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P = 3.1 × 10-6 ). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P = 0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.

U2 - 10.1002/hep4.1886

DO - 10.1002/hep4.1886

M3 - SCORING: Journal article

C2 - 34958182

VL - 6

SP - 1213

EP - 1226

JO - HEPATOL COMMUN

JF - HEPATOL COMMUN

SN - 2471-254X

IS - 5

ER -