Yan X H, Wu J L, Yu R, Ma X H, Li Q F, Xie R F
Department of Clinical Laboratory, Changsha Central Hospital Affiliated to Nanhua University, Changsha 410004, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2022 Feb 6;56(2):185-191. doi: 10.3760/cma.j.cn112150-20210818-00802.
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 C>G, C>G, and T>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% 70.79%, χ=7.109, =0.008), while the logarithm of ALT was significantly lower than that of the control group (1.78±0.43 1.95±0.54, =3.801, =0.000). The genotypes distributions of , , and 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, >0.05 for each). Among the subjects infected with HBV genotype C, CC ( TT) significantly increased the risk of HBV-LC [odds ratio () = 1.40, 95% confidence interval (): 1.03-1.91]. Among the HBV-infected subjects with HBeAg negative, GG genotype ( CC) and G allele ( C) significantly increased the risks of HBV-LC ( = 2.17, 95%: 1.11-4.23; = 1.45, 95%: 1.06-1.97, respectively). Haplotypes analysis showed that the frequency of haplotype C-G-T composed of , , and was significantly lower in HBV-LC than that in the control group (non-LC) (27.3% 35.6%, χ²=9.949, = 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 C-G-T of STAT3 gene have significantly decreased risk of LC.
探讨乙型肝炎病毒（HBV）感染后信号转导和转录激活因子3（STAT3）基因多态性与肝硬化（LC）的关联。选取2018年1月至2020年9月在南华大学附属长沙中心医院收集的243例乙型肝炎肝硬化患者（HBV-LC，病例组）和486例未发生肝硬化的HBV感染者（非LC，对照组）进行病例对照研究。通过文献及生物信息数据库筛选出STAT3基因的3个单核苷酸多态性（SNP）位点，分别为C>G、C>G和T>C，采用实时荧光定量PCR（RFQ-PCR）法检测其基因型。采用卡方检验比较两组间STAT3 SNP基因型的分布差异，通过Shesis在线软件进行单倍型分析。HBV-LC患者中HBV C基因型比例显著高于对照组（80.91%对70.79%，χ²=7.109，P=0.008），而丙氨酸氨基转移酶（ALT）对数显著低于对照组（1.78±0.43对1.95±0.54，t=3.801，P=0.000）。总体分析及按性别分层分析中，HBV-LC组与非LC组的rs7574865、rs3796428和rs3796429基因型分布差异均无统计学意义（χ²值分别为2.610、1.505、0.586、2.653、2.685、1.583、0.351、5.388、0.339，均P>0.05）。在感染HBV基因型C的受试者中，rs7574865位点CC（rs3796429位点TT）显著增加HBV-LC风险[比值比（OR）=1.40，95%置信区间（CI）：1.03 - 1.91]。在HBeAg阴性的HBV感染者中，rs3796428位点GG基因型（rs3796429位点CC）及G等位基因（rs3796429位点C等位基因）显著增加HBV-LC风险（OR分别为2.17，95%CI：1.11 - 4.23；OR为1.45，95%CI：1.06 - 1.97）。单倍型分析显示，由rs7574865、rs3796428和rs3796429组成的单倍型C-G-T在HBV-LC组中的频率显著低于对照组（非LC组）（27.3%对35.6%，χ²=9.949，P=0.001）。不同感染状态的HBV感染者中，STAT3与HBV-LC的相关性不同。携带STAT3基因单倍型C-G-T的HBV感染者发生LC的风险显著降低。
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