Apolipoprotein epsilon3 allele is associated with persistent hepatitis C virus infection

Host genetic factors may significantly influence the ability to clear hepatitis C virus (HCV) following infection. HCV is associated with very low density lipoproteins (VLDL) and low density lipoproteins (LDL) in the host's circulation. Apolipoprotein E (APOE) is found in VLDL and binds to potential receptors involved in HCV entry into cells, the LDL receptor, and the scavenger receptor protein SR-B1. The APOE gene is polymorphic with three alleles coding for three isoforms: Apo-epsilon2, Apo-epsilon3, and Apo-epsilon4. The aim of this study was to assess if these functional polymorphisms determine disease outcome in HCV infected individuals.

The APOE genotype was determined in 420 Northern European patients with evidence of exposure to HCV. Genotype and allele distribution were compared with those of 288 healthy controls and progression of liver disease and viral clearance were analysed according to APOE allele status.

The APOE*E2 and APOE*E4 alleles were both associated with a reduced likelihood of chronic infection (odds ratio (OR) 0.39 (95% confidence interval (CI) 0.211-0.728), p = 0.003; and OR 0.6 (95% CI 0.38-0.96), p = 0.032) and there was a notable absence of the E2E2 genotype in the HCV antibody positive group compared with the control population (p = 0.0067). Overall the genotypes carrying the E2 allele (E2,E3 and E2,E4) were associated with the equivalent of a 3-5-fold reduction in the risk of chronic HCV infection (genotype relative risk 0.36 and 0.20, respectively).

This study indicates that functional APOE gene polymorphisms may be a determinant of outcome in HCV infection. We hypothesise that the E2 allele may protect against viral persistence via defective binding of HCV lipoviral particles to the cellular receptors involved in entry of these infectious particles.