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Apolipoprotein E allele frequencies in chronic and self‐limited hepatitis C suggest a protective effect of APOE 4 in the course of hepatitis C virus infection
Author(s) -
Mueller Tobias,
Fischer Janett,
Gessner Reinhard,
Rosendahl Jonas,
Böhm Stephan,
Bömmel Florian,
Knop Viola,
Sarrazin Christoph,
Witt Heiko,
Marques Andreas Mas,
Kovacs Peter,
Schleinitz Dorit,
Stumvoll Michael,
Blüher Matthias,
Bugert Peter,
Schott Eckart,
Berg Thomas
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13094
Subject(s) - apolipoprotein e , hepatitis c virus , allele , genotype , single nucleotide polymorphism , immunology , hepatitis c , apolipoprotein b , allele frequency , ldl receptor , snp , medicine , biology , lipoprotein , virology , virus , disease , cholesterol , genetics , gene
Background & Aims 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 ( SNP s) 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 SNP s in two large and independent cohorts of patients with chronic HCV infection compared to respective controls. Methods 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. Results 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 APOE 4 alleles in chronically HCV ‐infected patients (10.2%) compared to 13.0% in healthy controls ( P = 0.001). The distribution of APOE 4 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 APOE 4 allele in HCV infection. This was confirmed by a significant over‐representation of the APOE 4 allele in patients with spontaneous HCV clearance (17.6%; P = 0.00008). The APOE 4 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. Conclusions Our findings suggest that the APOE 4 allele may confer a protective effect in the course of HCV infection.