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Association of polymorphism rs1053005 in STAT3 with chronic hepatitis B virus infection in Han Chinese population.

ABSTRACT: BACKGROUND:Signal transducer and activator of transcription 3 (STAT3) is involved in hepatitis B virus (HBV) infection and HBV-related hepatocellular carcinoma (HCC). The association between polymorphism rs1053005 and haplotypes formed by rs1053004 and rs1053005 in the 3'UTR of STAT3 and chronic HBV infection has yet to be investigated. METHODS:This study included 567 patients with chronic HBV infection (239 chronic hepatitis, 141 liver cirrhosis and 187 HCC), 98 HBV infection resolvers, and 169 healthy controls. STAT3 rs1053004 and rs1053005 polymorphisms were genotyped by TaqMan SNP Genotyping Assays. RESULTS:The rs1053004 genotype CC [P value by Bonferroni correction (P c )?=?0.002] and allele C (P c ?=?0.019) were more frequent in patients with chronic HBV infection than in healthy controls. The rs1053005 genotype GG was also more frequent in patients with chronic HBV infection than in healthy controls (P c ?=?0.046). The rs1053004-rs1053005 haplotype T-G was less frequent in patients with chronic HBV infection than in healthy controls (Pc?

SUBMITTER: Li M

PROVIDER: S-EPMC5879595 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Association of polymorphism rs1053005 in STAT3 with chronic hepatitis B virus infection in Han Chinese population.

Li Man M Li Fang F Li Na N Sang Jiao J Fan Xiude X Deng Huan H Zhang Xiaoge X Han Qunying Q Lv Yi Y Liu Zhengwen Z

BMC medical genetics 20180402 1

<h4>Background</h4>Signal transducer and activator of transcription 3 (STAT3) is involved in hepatitis B virus (HBV) infection and HBV-related hepatocellular carcinoma (HCC). The association between polymorphism rs1053005 and haplotypes formed by rs1053004 and rs1053005 in the 3'UTR of STAT3 and chronic HBV infection has yet to be investigated.<h4>Methods</h4>This study included 567 patients with chronic HBV infection (239 chronic hepatitis, 141 liver cirrhosis and 187 HCC), 98 HBV infection res ...[more]

PMID: 29609539

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Project description:Hepatocellular carcinoma associated with chronic hepatitis B virus infection seriously affects human health. Present studies suggest that genetic susceptibility plays an important role in the mechanism of cancer development. Therefore, this study focused on single nucleotide polymorphisms (SNPs) of MMR genes associated with HBV-HCC. Five groups of participants were included in this study, which were healthy control group (HC), spontaneous clearance (SC), chronic hepatitis B group (CHB), HBV-related liver cirrhosis group (LC) and HBV-related hepatocellular carcinoma group (HBV-HCC). A total of 3128 participants met the inclusion and exclusion criteria for this study. 20 polymorphic loci on MSH2, MSH3 and MSH6 were selected for genotyping. There were four case-control studies, which were HC vs. HCC, SC vs. HCC, CHB vs. HCC and LC vs. HCC. We used Hardy-Weinberg equilibrium test, unconditional logistic regression, haplotype analysis, and gene-gene interaction for genetic analysis. Ultimately, after excluding confounding factors such as age, gender, smoking and drinking, 12 polymorphisms were found to be associated with genetic susceptibility to HCC. Haplotype analysis showed the risk haplotype GTTT (rs1805355_G, rs3776968_T, rs1428030_C, rs181747_C) was more frequent in the HCC group compared with the HC group. The GMDR analysis showed that the best interaction model was the three-factor model of MSH2-rs1981928, MSH3-rs26779 and MSH6-rs2348244 in SC vs. HCC group (P=0.001). In addition, we found multiplicative or additive interactions between genes in our selected SNPs. These findings provide new ideas to further explore the etiology and pathogenesis of HCC. We have attempted to explain the molecular mechanisms by which certain SNPs (MSH2-rs4952887, MSH3-rs26779, MSH3-rs181747 and MSH3-rs32950) affect genetic susceptibility to HCC from the perspectives of eQTL, TFBS, cell cycle and so on. We also explained the results of haplotypes and gene-gene interactions. These findings provide new ideas to further explore the etiology and pathogenesis of HCC.

Dataset Information

Association of polymorphism rs1053005 in STAT3 with chronic hepatitis B virus infection in Han Chinese population.

Publications

Association of polymorphism rs1053005 in STAT3 with chronic hepatitis B virus infection in Han Chinese population.

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