TY - JOUR
T1 - PCSK9, apolipoprotein E and lipoviral particles in chronic hepatitis C genotype 3
T2 - evidence for genotype-specific regulation of lipoprotein metabolism
AU - Bridge, Simon
AU - Sheridan, David
AU - Felmlee, Daniel
AU - Crossey, Mary
AU - Fenwick, Fiona
AU - Lanyon, Clare
AU - Dubuc, Geneviève
AU - Seidah, Nabil
AU - Davignon, Jean
AU - Thomas, Howard
AU - Taylor-Robinson, Simon
AU - Toms, Geoffrey
AU - Neely, Robert Dermot
AU - Bassendine, Margaret
N1 - Available online ahead of print.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Background & Aims
Hepatitis C virus (HCV) associates with lipoproteins to form “lipoviral particles” (LVPs) that can facilitate viral entry into hepatocytes. Initial attachment occurs via heparan sulphate proteoglycans and low-density lipoprotein receptor (LDLR); CD81 then mediates a post-attachment event. Proprotein convertase subtilisin kexin type 9 (PCSK9) enhances the degradation of the LDLR and modulates liver CD81 levels. We measured LVP and PCSK9 in patients chronically infected with HCV genotype (G)3. PCSK9 concentrations were also measured in HCV-G1 to indirectly examine the role of LDLR in LVP clearance.
Methods
HCV RNA, LVP (d 1.07 g/ml) fractions, were quantified in patients with HCV-G3 (n = 39) by real time RT-PCR and LVP ratios (LVPr; LVP/(LVP + non-LVP)) were calculated. Insulin resistance (IR) was assessed using the homeostasis model assessment of IR (HOMA-IR). Plasma PCSK9 concentrations were measured by ELISA in HCV-G3 and HCV-G1 (n = 51).
Results
In HCV-G3 LVP load correlated inversely with HDL-C (r = −0.421; p = 0.008), and apoE (r = −0.428; p = 0.013). The LVPr varied more than 35-fold (median 0.286; range 0.027 to 0.969); PCSK9 was the strongest negative predictor of LVPr (R2 = 16.2%; p = 0.012). HOMA-IR was not associated with LVP load or LVPr. PCSK9 concentrations were significantly lower in HCV-G3 compared to HCV-G1 (p
AB - Background & Aims
Hepatitis C virus (HCV) associates with lipoproteins to form “lipoviral particles” (LVPs) that can facilitate viral entry into hepatocytes. Initial attachment occurs via heparan sulphate proteoglycans and low-density lipoprotein receptor (LDLR); CD81 then mediates a post-attachment event. Proprotein convertase subtilisin kexin type 9 (PCSK9) enhances the degradation of the LDLR and modulates liver CD81 levels. We measured LVP and PCSK9 in patients chronically infected with HCV genotype (G)3. PCSK9 concentrations were also measured in HCV-G1 to indirectly examine the role of LDLR in LVP clearance.
Methods
HCV RNA, LVP (d 1.07 g/ml) fractions, were quantified in patients with HCV-G3 (n = 39) by real time RT-PCR and LVP ratios (LVPr; LVP/(LVP + non-LVP)) were calculated. Insulin resistance (IR) was assessed using the homeostasis model assessment of IR (HOMA-IR). Plasma PCSK9 concentrations were measured by ELISA in HCV-G3 and HCV-G1 (n = 51).
Results
In HCV-G3 LVP load correlated inversely with HDL-C (r = −0.421; p = 0.008), and apoE (r = −0.428; p = 0.013). The LVPr varied more than 35-fold (median 0.286; range 0.027 to 0.969); PCSK9 was the strongest negative predictor of LVPr (R2 = 16.2%; p = 0.012). HOMA-IR was not associated with LVP load or LVPr. PCSK9 concentrations were significantly lower in HCV-G3 compared to HCV-G1 (p
KW - Apolipoprotein A1
KW - Apolipoprotein E
KW - HCV lipoviral particles
KW - HDL-C
KW - Low-density lipoprotein receptor
KW - PCSK9
U2 - 10.1016/j.jhep.2014.11.016
DO - 10.1016/j.jhep.2014.11.016
M3 - Article
SN - 0168-8278
SN - 0270-9319
SN - 1600-0641
VL - 62
SP - 763
EP - 770
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -