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Article Dans Une Revue International Hepatology Communications Année : 2022

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

1 GCU - Glasgow Caledonian University
2 UON - University of Nottingham, UK
3 University Hospital Bonn
4 Universität Bonn = University of Bonn
5 Heidelberg University Hospital [Heidelberg]
6 Big Data Institute - Nuffield Department of Medicine [Oxford, UK]
7 University Hospital Leipzig = Universitätsklinikum Leipzig
8 MLU - Martin-Luther-Universität Halle Wittenberg
9 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
10 UNIL - Université de Lausanne = University of Lausanne
11 UCL - Université Catholique de Louvain = Catholic University of Louvain
12 MIVEGEC - Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle
13 UKS - Saarland University Hospital
14 Saarland University [Saarbrücken]
15 University of Glasgow
16 Universität Heidelberg [Heidelberg] = Heidelberg University
17 Medizinische Universität Wien = Medical University of Vienna
18 PMU - Paracelsus Medizinische Privatuniversität = Paracelsus Medical University
19 MRI TUM - Klinikum rechts der Isar
20 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
21 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
22 OVGU - Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg]
23 MHH - Medizinische Hochschule Hannover = Hannover Medical School
24 UKSH - University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein
25 University Hospital Carl Gustav Carus [Dresden, Germany]
26 Goethe University Frankfurt
27 EF CLIF - European Foundation for Study of Chronic Liver Failure [Barcelona]
28 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
29 UNIMI - Università degli Studi di Milano = University of Milan
30 University Medical Center Rostock
31 ULB - Hôpital Erasme [Bruxelles]
32 Cliniques universitaires St Luc [Bruxelles]
33 University hospital of Zurich [Zurich]
Indra Neil Guha

Résumé

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.

Dates et versions

hal-03691807 , version 1 (09-06-2022)

Identifiants

Citer

Hamish Innes, Hans Dieter Nischalke, Indra Neil Guha, Karl Heinz Weiss, Will Irving, et al.. The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis. International Hepatology Communications, 2022, 6 (5), pp.1213-1226. ⟨10.1002/hep4.1886⟩. ⟨hal-03691807⟩
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