title: Apolipoprotein E allele frequencies in chronic and self-limited hepatitis C suggest a protective effect of APOE4 in the course of hepatitis C virus infection.
abstract: Infectious hepatitis C virus (HCV) particles bind to host lipoproteins such as low-density lipoproteins (LDLs). Low-density lipoprotein receptors (LDLR) have been termed candidate receptors for HCV-LDL complexes. Functional host genetic single nucleotide polymorphisms (SNPs) in the apolipoprotein E (APOE) gene encoding apolipoprotein E (apoE) - a major structural LDL component and natural ligand of LDLR - likely influence the course of HCV infection. We investigated the prevalence of APOE SNPs in two large and independent cohorts of patients with chronic HCV infection compared to respective controls.
  
  
  
  We genotyped 996 chronically HCV-infected patients; 179 patients with spontaneous HCV clearance; 283 individuals with non-HCV-associated liver disease; and 2 234 healthy controls.
  
  
  
  APOE genotype proportions in patients with persistent HCV infection significantly differed from healthy controls (P = 0.007) primarily because of a substantial under-representation of APOE4 alleles in chronically HCV-infected patients (10.2%) compared to 13.0% in healthy controls (P = 0.001). The distribution of APOE4 allele positive genotypes (ε2ε4, ε3ε4, ε4ε4) also significantly differed between chronically HCV-infected patients and healthy controls (1.4%, 17%, 1% vs. 2.4%, 20.5%, 1.7%; P = 0.001), suggesting a protective effect of the APOE4 allele in HCV infection. This was confirmed by a significant over-representation of the APOE4 allele in patients with spontaneous HCV clearance (17.6%; P = 0.00008). The APOE4 allele distribution in patients with non-HCV-associated liver disease (14.0%) was very similar to healthy controls and also differed from chronically HCV-infected patients (P = 0.012), suggesting HCV specificity.
  
  
  
  Our findings suggest that the APOE4 allele may confer a protective effect in the course of HCV infection.
authors.affiliation: Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Mueller
authors.affiliation: Sektion Hepatologie, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum, Leipzig, Germany.
authors.forename: Janett
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Klinik für Visceral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Gessner
authors.affiliation: Department of Internal Medicine I, Martin Luther University, Halle, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Rosendahl
authors.affiliation: Sektion Hepatologie, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum, Leipzig, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Böhm
authors.affiliation: Sektion Hepatologie, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum, Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: van Bömmel
authors.affiliation: Medizinische Klinik I, Universitätsklinikum der Johann Wolfgang-Goethe Universität, Frankfurt, Germany.
authors.forename: Viola
authors.initials: V
authors.lastname: Knop
authors.affiliation: Medizinische Klinik I, Universitätsklinikum der Johann Wolfgang-Goethe Universität, Frankfurt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Kinderklinik und Poliklinik, Technische Universität München (TUM), München, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Witt
authors.affiliation: Robert Koch-Institut, Berlin, Germany.
authors.forename: Andreas Mas
authors.initials: AM
authors.lastname: Marques
authors.affiliation: IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.affiliation: IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: Dorit
authors.initials: D
authors.lastname: Schleinitz
authors.affiliation: IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.affiliation: IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service of Baden-Württemberg-Hessen, Mannheim, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.affiliation: Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Schott
authors.affiliation: Sektion Hepatologie, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005355:Fibrosis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005858:Germany; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000235:genetics*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C000612345:ApoE protein, human; D001057:Apolipoproteins E; D008077:Lipoproteins, LDL
keywords: hepatic fibrosis; hepatic steatosis; lipoprotein; low-density lipoprotein receptor; spontaneous HCV resolution