APOB codon 4311 polymorphism is associated with hepatitis C virus infection through altered lipid metabolism

Abstract

BackgroundIt has been reported that some single-nucleotide polymorphisms (SNPs) in lipid regulators such as apolipoproteins and cell surface molecules for hepatitis C virus (HCV) entry into hepatocytes are associated with HCV infection. However, it is unknown how HCV infection is affected by altered lipid metabolism resulting from the SNPs. We investigated the relationship between these SNPs and HCV infection status, and also analyzed the mechanism by which these SNPs mediate HCV infection via lipid metabolism alterations.MethodsSerum lipid and apolipoprotein profiles were tested in 158 HCV-positive and 220 HCV-negative subjects. We selected 22 SNPs in five lipid regulator genes which were related to HCV entry into hepatocytes and to lipid metabolism (APOA1, APOB, SR-B1, LDLR, and APOE), and their polymorphisms were analyzed using the PCR-sequence-specific oligonucleotide probe-Luminex method.ResultsAn APOB N4311S (g.41553a > g) SNP, rs1042034, was significantly associated with HCV positivity; the HCV positivity rate for the minor allele AA genotype was significantly higher than for genotype AG + GG (P = 0.016). Other SNPs except for APOB P2712L SNP rs676210, which is in linkage disequilibrium with rs1042034, showed no significant difference in genotype distribution. The serum level of low density lipoprotein-cholesterol (LDL-C) in the genotype AA group was significantly lower than in the genotype non-AA group (P = 0.032), whereas the triglyceride (TG) level was significantly higher (P = 0.007).ConclusionAn APOB SNP, rs1042034, is closely associated with HCV infection through lipid metabolism alteration. The minor allele AA genotype might contribute to facilitating serum LDL uptake into hepatocytes via LDLR by modifying their affinity and interaction and may have an influence on HCV infection by their entry to the liver through the LDLR.

A genome‐wide association study on low susceptibility to hepatitis C virus infection (GEHEP012 study)

“…In accordance with previous studies, it seems that the different susceptibility to HCV infection could be driven by multiple genetic factors, each with low to moderate effect size. In this study, we have validated the reported direction of effects of rs5925 and rs688 polymorphisms within LDLR gene .…”

“…Several studies have been performed in the last years to detect genetic variants associated with different susceptibility to HCV infection. Specifically, polymorphisms linked to LDLR , LDLRAP1 , APOB , RELA , IL12B and CD209 genes have been previously associated with this trait. Taken together, these findings suggest that susceptibility to HCV infection might be a multigenetic condition.…”

Hepatitis C Virus (HCV)–Apolipoprotein Interactions and Immune Evasion and Their Impact on HCV Vaccine Design

“…A follow-up study reported that the rs12979860 CC responder genotype was associated with higher serum levels of ApoB, suggesting that alteration of ApoB levels are part of the IFN response ( 68 ). Moreover, a recent study showed that the ApoB polymorphism rs1042034 is significantly associated with the HCV infection status ( 69 ). The AA allele, which was characterized by significantly lower serum levels of LDL-cholesterol, might contribute to facilitating serum LDL uptake into human hepatocytes.…”

Genetic Susceptibility to Chronic Liver Disease in Individuals from Pakistan

“…All this together suggests that APOB is deeply involved in the HCV life cycle [58]. Many studies investigated the genetic association between APOB and HCV-related viral disease showing that variants in APOB increase the susceptibility to HCV infection [59,60]. So far, variants on APOB were mainly investigated for associations with cardiovascular disease showing a different effect based on population ethnicity [61].…”