P787 HEPATIC EXPRESSION OF miRNA AND miR-33a TARGET GENES IN CHRONIC HCV INFECTION

Background and Aims: Several miRNAs have been described to finely regulate lipid metabolism including, miR-33, miR-122. miR33a represents one of the most interesting and attractive targets for metabolic-related. The identification of ABCA1 and NPC1 as miR-33 target genes leads to the hypothesis that miR-33 may be regulating high-density lipoproteins (HDL) levels in vivo. The hepatitis C virus (HCV) requires elements of host lipid metabolism to replicate. Our purpose was measure hepatic levels of miR-33a, miR-122 and miR33a target genes in HCV infection. Methods: Liver biopsies from 62 treatment-naive patients with chronic Hepatitis C were included (48 infected by HCV-1 and 14 infected by HCV-3). After isolation of total RNA, a miRNA expression assay was performed to detect expression. At the same time, a gene expression assays were performed to investigate mRNA expression changes in miRNA target genes (NPC1, ABCA-1 and CPT1). Results: In patients infected by HCV-3, a positive correlation was found between hepatic miR-33a expression and serum cholesterol (p = 0.0306; r = 0.5548). In addition, miR-33a expression also was correlated to NPC1 gene expression (p =0.0439; r = 0.5134). A significant negative correlation between hepatic NPC1 and CPT1 expression and the levels of serum APO-E was observed in HCV-1 infection (p =0.0076; r = −0.3805 and p=0.0242; r = −0.3250, respectively). Conclusions: HCV infection leads to the expression of genes involved in biosynthesis and transport of lipids, creating a favorable environment for virus replication. A better understanding of the mechanisms that underlie miR-33-mediated coupled with improvements in drug delivery technology, will definitely enable miR-33-mediated therapy to open a new area.