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Association of Polymorphism in Pri-microRNAs-371-372-373 with the Occurrence of Hepatocellular Carcinoma in Hepatitis B Virus Infected Patients

Cited 21 time in Web of Science Cited 23 time in Scopus
Authors

Kwak, Min-Sun; Lee, Dong Hyeon; Cho, Yuri; Cho, Eun-Ju; Lee, Jeong-Hoon; Yu, Su Jong; Yoon, Jung-Hwan; Lee, Hyo-Suk; Kim, Chung Yong; Cheong, Jae Youn; Cho, Sung Won; Shin, Hyoung Doo; Kim, Yoon Jun

Issue Date
2012-07
Publisher
Public Library of Science
Citation
PLoS ONE, Vol.7 No.7
Abstract
Background: Micro RNAs-371-372-373 (miRNAs-371-373), originating from the same pri-miRNA transcript, are reported to be upregulated in hepatocellular carcinoma (HCC) and to be related to the regulation of hepatitis B virus (HBV) infection. Our study investigated whether pri-miRNAs-371-373 polymorphisms are associated with the risk of HCC occurrence and HBV clearance. Methods: Genetic variations were identified through direct DNA sequencing using TaqMan assay. Three sequence variants of pri-miRNAs-371-373 were identified. Genetic associations of those with HCC occurrence and HBV clearance among patients with HBV infection were analyzed using logistic regression analyses with adjustment for age and gender (n = 1439). Results: For the occurrence of HCC, polymorphism rs3859501C > A acted as a protective factor both in chronic carriers (OR = 0.75, P = 0.005 in a codominant model; OR = 0.71, P = 0.02 in a dominant model; OR = 0.66, P = 0.03 in recessive model) and liver cirrhosis patients (OR = 0.69, P = 0.001 in a codominant model; OR = 0.60, P = 0.003 in a dominant model; OR = 0.63, P = 0.03 in a recessive model). The pri-miRNAs-371-373_ht2 [C-A-C] also showed a protective effect on HCC occurrence both in the chronic carrier and liver cirrhosis groups (P < 0.05 in both). However, there was no significant association between pri-miRNAs-371-373 polymorphisms and HBV clearance. Conclusions: In conclusion, among chronic carriers and liver cirrhosis patients, the A allele of rs3859501 and the haplotype pri-miRNAs-371-373_ht2 were more protective to HCC than other genotypes and haplotypes. Further studies into the roles of rs3859501 and pri-miRNAs-371-373_ht2 haplotype in hepatocarcinogenesis are needed.
ISSN
1932-6203
URI
https://hdl.handle.net/10371/180035
DOI
https://doi.org/10.1371/journal.pone.0041983
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