title: 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.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
authors.forename: Hwi Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D060467:Disease Resistance; D005260:Female; D005787:Gene Frequency; D060005:Genotyping Techniques; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C542543:MIRN196 microRNA, human; D035683:MicroRNAs
keywords: hepatitis B; liver cancer; microRNA; polymorphism