Association study of genetic variations in microRNAs with the risk of hepatitis B-related liver diseases.
OBJECTIVE
MicroRNAs have been recently identified as important regulators that influence human carcinogenesis, cancer progression, and the interaction between the host and virus. This study investigates an association between microRNAs (miR-101-1, miR-101-2, and miR-338) and the risk of liver diseases through clearance of hepatitis B virus infection, development of liver cirrhosis, and hepatocellular carcinoma occurrence.


METHODS
Genetic variations were genotyped using the TaqMan assay in 1439 Korean hepatitis B virus patients. To investigate the relationship between four polymorphisms in three microRNAs and the disease phenotypes, differences in frequency distribution of variations were analysed using logistic and multiple regression analyses after adjusting for age and gender as covariates.


RESULTS
We find that the rs7536540 polymorphism in miR-101-1 is significantly associated with development of liver cirrhosis and hepatocellular carcinoma occurrence. In addition, rs12375841 and its unique haplotype (ht2) in miR-101-2 show significant association with clearance of hepatitis B virus infection.


CONCLUSIONS
To our knowledge, this is the first study to examine a relationship between the three microRNA genes and the risk of hepatitis B-related liver diseases. We expect that the findings in this study will be helpful to further genetic studies in the pathophysiology of hepatitis B virus-related liver diseases.
Laboratory of Genomic Diversity, Department of Life Science, Sogang University, Shinsudong, Mapo-gu, Seoul, Republic of Korea.
Joon Seol
JS
Bae
Jeong-Hyun
JH
Kim
Charisse Flerida A
CF
Pasaje
Hyun Sub
HS
Cheong
Tae Hoon
TH
Lee
In Song
IS
Koh
Hyo-Suk
HS
Lee
Yoon Jun
YJ
Kim
Hyoung Doo
HD
Shin
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006509:Hepatitis B / Q000150:complications / Q000235:genetics*; D006515:Hepatitis B virus; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012307:Risk Factors; D019914:Taq Polymerase; D055815:Young Adult
D035683:MicroRNAs; D019914:Taq Polymerase