title: A miR-1231 binding site polymorphism in the 3'UTR of IFNAR1 is associated with hepatocellular carcinoma susceptibility.
abstract: Hepatocellular carcinoma (HCC) is a common liver malignancy worldwide and genetic factors play important roles in the pathogenesis of HCC. Based on in-silico analysis, a case-control study including 420 HCC patients and 420 healthy controls was conducted to investigate the association between HCC susceptibility with a 4-bp insertion/deletion polymorphism (rs17875871) in the 3'UTR of IFNAR1. Computational modeling suggested that rs17875871 was located in seed region of miR-1231 potential target sequence in IFNAR1 3'UTR. Logistic regression analysis showed that the heterozygote and the 4-bp del/del homozygote genotypes confer significantly higher risks of HCC (adjusted OR=1.35, 95% CI=1.01-1.83, P=0.045; OR=1.84, 95% CI=1.18-2.84, P=0.006, respectively). Stratification analysis revealed that this association was more pronounced in HBsAg positive subgroup. Our findings suggested common genetic changes in IFNAR1 may influence HCC risk, likely through miR-1231-mediated regulation, which is possibly involved in the pathogenesis of HBV related HCC. Further replication studies and functional characterization of rs17875871 were needed to fully clarify the underlined molecular mechanism.
authors: Department of Gastroenterology, Suzhou Municipal Hospital, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215002, Jiangsu, China.
authors: Chunxiao
authors: C
authors: Zhou
authors: Qiang
authors: Q
authors: Yu
authors: Lei
authors: L
authors: Chen
authors: Jian
authors: J
authors: Wang
authors: Shudan
authors: S
authors: Zheng
authors: Jinkun
authors: J
authors: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D053633:Receptor, Interferon alpha-beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C507964:IFNAR1 protein, human; C576014:MIRN1231 microRNA, human; D035683:MicroRNAs; D053633:Receptor, Interferon alpha-beta