MicroRNA-196A-2 polymorphisms and hepatocellular carcinoma in patients with chronic hepatitis B

Abstract

Single nucleotide polymorphisms (SNPs) in microRNA (miR)-196a-2 have been

suggested to contribute to susceptibility to various human cancers. The aim of

this study was to determine whether polymorphisms of miRNA-196a-2 affect the

clinical outcomes of hepatitis B virus (HBV) infection in Korean patients.

Genotyping was performed for 1,439 Korean patients with either past or present

HBV infection, including 404 control subjects who underwent spontaneous recovery

and 1,035 subjects with chronic HBV (313 cases of chronic hepatitis B, 305 cases

of cirrhosis of the liver, and 417 cases of hepatocellular carcinoma [HCC]).

Genotyping results revealed that the polymorphism rs12304647A>C, which lies in

the pri-miRNA region of miR-196a-2, has a significant minor allele frequency

(0.210). Logistic analysis revealed that the rs12304647A>C SNP was associated

with a significant protective effect against HCC in patients with chronic

hepatitis (odds ratio [OR] = 0.70, P = 0.005 in a codominant model; OR = 0.73, P

= 0.03 in a dominant model; OR = 0.31, P = 0.004 in a recessive model), and in

the patients with cirrhosis (OR = 0.63, P = 0.0009 in a codominant model; OR =

0.66, P = 0.01 in a dominant model; OR = 0.25, P = 0.001 in a recessive model). A

Cox relative hazards model with adjustments for age, gender, HBeAg status, and

cirrhosis revealed that rs12304647A>C retained its association with HCC in a

codominant model (relative hazards [RH] = 1.14, P = 0.05) and in a recessive

model (RH = 1.44, P = 0.03). However, the miR-196a-2 rs12304647A>C SNP had no

association with HBV clearance. In conclusion, the miR-196a-2 rs12304647 CC

genotype had a protective effect against development of HCC in comparison to the

AA or AC genotypes in patients with chronic hepatitis and cirrhosis.