Association of polymorphism in microRNA 604 with susceptibility to persistent hepatitis B virus infection and development of hepatocellular carcinoma.

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.