title: MicroRNA-122 associates with serum apolipoprotein B but not liver fibrosis markers in CHC genotype 1 infection.
abstract: miR-122 is the predominant liver miRNA that regulates hepatic lipid metabolism and inflammation. Hepatitis C virus (HCV) modulates host intracellular lipid metabolism. HCV stability and propagation also depend on an interaction between virus and miR-122. Our aims were to examine the associations between miR-122, apolipoproteins, and serum makers of fibrosis in chronic hepatitis C (CHC) patients. We evaluated baseline sera from 36 CHC genotype 1 patients who completed the Phase IIa study of miravirsen (LNA oligonucleotide targeting miR-122). Samples were assessed for liver transaminases, IL 28B genotype, IP-10, and lipid profiles. The noninvasive markers of liver fibrosis, APRI, and FIB-4, were calculated using standard formulae. miR-122 levels were measured using RT-PCR and expressed as fold-change compared to normal healthy controls. CHC patients were mostly male (61%) with mean age 47.5 ± 11.6 years. Patients with higher ApoB (ApoB/ULN ≥ 0.5) has significantly lower miR-122 levels in compared to patients with lower ApoB (ApoB/ULN < 0.5). (8.28 ± 6.23 vs. 16.28 ± 13.71; P = 0.02). There were no similar associations between miR-122 and ApoA-1 or between HCV RNA and lipoproteins. There were no differences in miR-122 levels between patients with different stages of fibrosis determined by APRI or FIB-4. Patients with lower ApoB had higher serum miR-122 levels. However, we cannot identify significant association between miR-122, ApoA-1, or fibrosis markers in this small cohort of CHC genotype 1 patients. The mechanism of HCV dyslipidemia is complex and could partly relate to the effect of miR-122 on lipid metabolism which requires further evaluation in a larger study.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Bassem
authors.initials: B
authors.lastname: Matta
authors.affiliation: Santaris Pharma A/S, San Diego, California.
authors.forename: Bernard D
authors.initials: BD
authors.lastname: King
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hodges
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina.|Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Tillmann
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina.|Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000235:genetics; D001055:Apolipoproteins B / Q000097:blood* / Q000235:genetics; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood / Q000235:genetics; D050171:Dyslipidemias / Q000821:virology; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008103:Liver Cirrhosis / Q000235:genetics / Q000276:immunology / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009841:Oligonucleotides; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C581159:miravirsen
keywords: apolipoprotein; cholesterol; fibrosis markers; hepatitis C virus; microRNA