To investigate the associations between gene polymorphisms of signal transducer and activator of transcription 3 (STAT3) and liver cirrhosis (LC) after hepatitis B virus (HBV) infection. A case-control study was conducted in 243 patients with hepatitis B cirrhosis (HBV-LC, case group) and 486 HBV-infected subjects without LC (non-LC, control group) collected from January 2018 to September 2020 at the Changsha Central Hospital Affiliated to Nanhua University. Three single nucleotide polymorphisms (SNPs) of STAT3 gene, including rs4796793C>G, rs2293152C>G, and rs1053004T>C were selected through literature and biological information database, and the genotypes were detected by real-time fluorescent quantitative PCR (RFQ-PCR). The distribution differences of STAT3 SNPs genotypes between the two groups were compared using Chi-square test and haplotype analysis was conducted by Shesis online. The proportion of HBV C genotype in HBV-LC patients was significantly higher than that in the control group (80.91% vs. 70.79%, χ2=7.109, P=0.008), while the logarithm of ALT was significantly lower than that of the control group (1.78±0.43 vs. 1.95±0.54, t=3.801, P=0.000). The genotypes distributions of rs4796793, rs2293152, and rs1053004 were not significantly different between HBV-LC and non-LC in overall analysis and stratified analysis by gender (χ²=2.610, 1.505, 0.586, 2.653, 2.685, 1.583, 0.351, 5.388, 0.339, respectively, P>0.05 for each). Among the subjects infected with HBV genotype C, rs1053004 CC (vs. TT) significantly increased the risk of HBV-LC [odds ratio (OR) = 1.40, 95% confidence interval (CI): 1.03-1.91]. Among the HBV-infected subjects with HBeAg negative, rs4796793 GG genotype (vs. CC) and G allele (vs. C) significantly increased the risks of HBV-LC (OR = 2.17, 95%CI: 1.11-4.23; OR = 1.45, 95%CI: 1.06-1.97, respectively). Haplotypes analysis showed that the frequency of haplotype C-G-T composed of rs4796793, rs2293152, and rs1053004 was significantly lower in HBV-LC than that in the control group (non-LC) (27.3% vs. 35.6%, χ²=9.949, P = 0.001). The correlation between STAT3 and HBV-LC is different in HBV-infected subjects with different infection status. The HBV-infected subjects carrying haplotype rs4796793C-rs2293152G-rs1053004T of STAT3 gene have significantly decreased risk of LC.
旨在探讨信号传导与转录激活因子3（signal transducer and activator of transcription 3，STAT3）基因多态性与乙型肝炎病毒（hepatitis B virus，HBV）感染后肝硬化（liver cirrhosis，LC）的相关性。本研究采用病例对照研究方法，以2018年1月至2020年9月在南华大学附属长沙市中心医院就诊的243例乙型肝炎肝硬化患者（HBV-LC，实验组）与486例非肝硬化HBV感染者（non-LC，对照组）为研究对象。通过文献和生物信息数据库选定3个STAT3基因单核苷酸多态性（single nucleotide polymorphisms，SNPs）（rs4796793C>G、rs2293152C>G、rs1053004T>C），使用荧光探针实时定量PCR法（real-time fluorescent quantitative PCR，RFQ-PCR）对SNPs基因型进行检测。采用χ²检验比较STAT3 SNPs各基因型在两组研究对象间的分布差异，使用SHEsis在线软件进行单倍型分析。结果显示，HBV-LC患者中HBV C基因型比例显著高于对照组（80.91% vs. 70.79%，χ²=7.109，P=0.008），而ALT对数值显著低于对照组（1.78±0.43 vs. 1.95±0.54，t=3.801，P=0.000）。rs4796793、rs2293152和rs1053004基因型分布在HBV-LC与non-LC两组人群总体及不同性别人群间差异均无统计学意义（χ²=2.610，1.505，0.586，2.653，2.685，1.583，0.351，5.388，0.339，P>0.05）。在C基因型HBV感染者中，rs1053004 CC基因型（vs. TT基因型）显著增加肝硬化的发病风险（OR=1.40，95%CI：1.03~1.91）。在HBeAg阴性HBV感染者中，rs4796793 GG基因型（vs. CC基因型）及G等位基因（vs. C等位基因）均显著增加肝硬化发病风险（OR=2.17，95%CI：1.11~4.23；OR=1.45，95%CI：1.06~1.97）。单倍型分析显示，由rs4796793、rs2293152和rs1053004构成的单倍型C-G-T在HBV-LC中的频率显著低于non-LC（27.3% vs. 35.6%，χ²=9.949，P=0.001）。综上，STAT3与HBV-LC的相关性在不同感染状态的HBV感染者中存在差异，携带STAT3基因单倍型rs4796793C-rs2293152G-rs1053004T的HBV感染者发生肝硬化的可能性较低。.