Association of a microRNA-323b polymorphism with the persistence of hepatitis B virus infection by the enhancement of viral replication

Abstract

Recent studies have shown that some mammalian microRNAs (miRNAs) play a role in

antiviral defence. However, little is known about the role of miRNA-323b in

hepatitis B virus (HBV)-host interaction. We explored whether single nucleotide

polymorphism (SNP) of miRNA-323b affects HBV replication in a Korean HBV cohort.

Genotyping was performed in a total of 1439 subjects composed of 404

spontaneously recovered (SR) subjects as normal controls and 1035 chronic

carriers (CC) of HBV who were further classified into 313 patients with chronic

hepatitis, 305 patients with liver cirrhosis and 417 patients with hepatocellular

carcinoma. To confirm the effect of SNP of miRNA-323b on HBV replication in

vitro, HepAD38 cells were transfected with miRNA-323b wild type or miRNA-323b SNP

plasmid vectors, and HBV replication was induced for 5 days. HBV DNA was isolated

and quantified using real-time PCR. The polymorphism rs56103835C>T in the

pre-miRNA region of miRNA-323b revealed significant minor allele frequency

(0.273). rs56103835C>T SNP showed significantly affect persistence of HBV in CC

group compared with SR group (OR = 1.29, P = 0.009 in a codominant model; OR =

1.29, P = 0.03 in a dominant model; and OR = 1.78, P = 0.03 in a recessive

model). In vitro, the total intracellular HBV DNA content was significantly

reduced by miRNA-323b wild-type plasmid vector transfection (P = 0.014). The

polymorphism of miRNA-323b was significantly associated with persistence of HBV

by the enhancement of HBV replication (P = 0.021). Our findings provide a novel

perspective on the role SNP of miRNAs in host-virus interactions in HBV

infection.