title: Contributions of polymorphisms in miR146a, miR196a, and miR499 to the development of hepatocellular carcinoma.
abstract: Hepatocellular carcinoma is one of the most common malignant tumors worldwide; it is estimated that there were 782,000 new cases in 2012. MicroRNAs (miRNAs) play an important role in carcinogenesis by regulating oncogenes and tumor suppressors. We investigated the role of miR-146a, miR-196a2, and miR-499 polymorphisms in the risk of hepatocellular carcinoma in a Chinese population. Hepatocellular carcinoma patients (175) and healthy controls (302) were recruited between April 2013 and March 2015. Genotype analysis of miR-146a, miR-196a2, and miR-499 polymorphisms was carried out by polymerase chain reaction-restriction fragment length polymorphism. There was a significant difference between the genotype distribution of miR-196a2 in hepatocellular carcinoma patients and controls (X2= 17.23, P < 0.001). CG and GG miR-146a genotypes significantly elevated the risk of hepatocellular carcinoma compared with the CC genotype, with adjusted ORs (95%CI) of 3.05 (1.07-8.70) and 4.96 (1.64-14.97), respectively. In the recessive model, the CG + GG genotype had a 3.75-fold risk of hepatocellular carcinoma compared with the CC genotype, with an adjusted OR (95%CI) of 3.75 (1.39-10.11). However, no significant association was observed between miR-196a2 and miR-499 variants and risk of hepatocellular carcinoma in the co-dominant, dominant, and recessive models. The miR-146a polymorphism is a G to C substitution that causes a mismatch in the stem-loop of miRNA, which influences how the expression and transcriptional regulation of miRNA affects its target genes. Our study revealed that the GG and CG genotypes of miR-146a increased the risk of hepatocellular carcinoma in the Chinese population.
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.|General Surgery Department, Taixing People's Hospital of Yangzhou University, Jiangsu, China.
authors.forename: L H
authors.initials: LH
authors.lastname: Zhang
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: B B
authors.initials: BB
authors.lastname: Hao
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: X Z
authors.initials: XZ
authors.lastname: Dai
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China zhangfengzf41@163.com.
authors.forename: F
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C542542:MIRN146 microRNA, human; C542543:MIRN196 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs