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.

The Clinical Application of MicroRNAs in Infectious Disease

“…miRNA regulation has been described in a wide range of leukocytes and in the innate immune responses of non-leukocytes ( 12 , 34 , 63 – 71 ). Indeed, single nucleotide polymorphisms in miRNA loci have been associated with susceptibility to leprosy and infection outcome in human cytomegalovirus (hCMV) and hepatitis B infection ( 72 – 76 ). Although confirming the functional nature of such associations is difficult, the findings of such studies are in keeping with the important role of miRNAs in immunity and provide some evidence that person to person variation in susceptibility to infection could be governed by polymorphism in miRNA genes, at least for certain pathogens.…”

Haplotype‐based association of two SNPs in miR‐323b with unexplained recurrent spontaneous abortion in a Chinese Han population

“…MiR‐323b‐5p was previously named miR‐453(Altuvia et al, ; Landgraf et al, ), but appears to be processed from the same hairpin. Recently published articles have demonstrated that rs56103835 in miR‐323b was associated with the persistence of hepatitis B virus infection by the enhancement of viral replication (Yu et al, ). Polymorphisms of protein coding genes in the hsa‐miR‐323b binding site have been identified to be associated with many diseases.…”

“…A recently published report showed that rs56103835 C>T in the pre‐miRNA region of miRNA‐323b was significantly associated with persistence of HBV by the enhancement of HBV replication (Yu et al, ). And it will be an interesting question whether SNPs in pre‐miR‐323b is related with other diseases.…”

MicroRNA-Related Polymorphisms in Infectious Diseases—Tiny Changes With a Huge Impact on Viral Infections and Potential Clinical Applications

“…Still considering Korean patients, Yu et al ( 80 ) evaluated the miR-323b A/C/T SNP (rs56103835) on HBV replication and clinical course of infection. In that study, miR-323b rs56103835 was associated with persistent infection and was hypothesized as a factor which facilitates chronic HBV infection.…”