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. 2022 Feb 6;56(2):185-191.
doi: 10.3760/cma.j.cn112150-20210818-00802.

[Associations between gene polymorphisms of signal transducer and activator of transcription 3 and the susceptibility to hepatitis B virus related liver cirrhosis]

[Article in Chinese]
Affiliations

[Associations between gene polymorphisms of signal transducer and activator of transcription 3 and the susceptibility to hepatitis B virus related liver cirrhosis]

[Article in Chinese]
X H Yan et al. Zhonghua Yu Fang Yi Xue Za Zhi. .

Abstract

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)。rs4796793rs2293152rs1053004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rs4796793rs2293152rs1053004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。.

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