J Korean Med Sci.  2014 Nov;29(11):1523-1527. 10.3346/jkms.2014.29.11.1523.

Association of Polymorphism in MicroRNA 604 with Susceptibility to Persistent Hepatitis B Virus Infection and Development of Hepatocellular Carcinoma

Affiliations
  • 1Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
  • 2Department of Life Science, Sogang University, Seoul, Korea.
  • 3Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. yoonjun@snu.ac.kr

Abstract

MicroRNA polymorphisms may be associated with carcinogenesis or immunopathogenesis of infection. We evaluated whether the mircoRNA-604 (miR-604) polymorphism can affect the persistence of hepatitis B virus (HBV) infection, and the development to hepatocellular carcinoma (HCC) in patients with chronic HBV infection. A total of 1,439 subjects, who have either past or present HBV infection, were enrolled and divided into four groups (spontaneous recovery, chronic HBV carrier without cirrhosis, liver cirrhosis and HCC). We genotyped the precursor miR-604 genome region polymorphism. The CC genotype of miR-604 rs2368392 was most frequently observed and T allele frequency was 0.326 in all study subjects. The HBV persistence after infection was higher in those subjects with miR-604 T allele (P=0.05 in a co-dominant and dominant model), which implied that the patients with miR-604 T allele may have a higher risk for HBV chronicity. In contrast, there was a higher rate of the miR-604 T allele in the chronic carrier without HCC patients, compared to those of the HCC patients (P=0.03 in a co-dominant model, P=0.02 in a recessive model). The T allele at miR-604 rs2368392 may be a risk allele for the chronicity of HBV infection, but may be a protective allele for the progression to HCC in chronic HBV carriers.

Keyword

Hepatitis B Virus; Carcinoma, Hepatocellular; MicroRNAs; Polymorphism

MeSH Terms

Adult
Aged
Aged, 80 and over
Base Sequence
Carcinoma, Hepatocellular/etiology/*genetics/pathology
Case-Control Studies
Demography
Female
Gene Frequency
*Genetic Predisposition to Disease
Genotype
Hepatitis B Antibodies/blood
Hepatitis B Surface Antigens/blood
Hepatitis B e Antigens/blood
Hepatitis B virus/metabolism
Hepatitis B, Chronic/complications/*genetics/virology
Humans
Liver Neoplasms/etiology/*genetics/pathology
Male
MicroRNAs/*genetics/metabolism
Middle Aged
Polymorphism, Single Nucleotide
Risk Factors
Hepatitis B Antibodies
Hepatitis B Surface Antigens
Hepatitis B e Antigens
MicroRNAs

Figure

  • Fig. 1 Nucleotide sequence of miR-604 on chromosome 10p11.23. rs2368392 is marked with arrow head. The frequency in parentheses was based on the genotyping data (n = 1,439). The mature miRNA sequence is underlined.


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