血清DNMT1、TIM-3、QSOX1在妊娠合并HBV感染患者中的表达水平及与母婴不良结局的关系

Serum levels of DNMT1, TIM-3, and QSOX1 in pregnant women with HBV infection and their associations with adverse maternal and neonatal outcomes

摘要:

目的 探究血清脱氧核糖核酸甲基转移酶1（DNMT1）、T细胞免疫球蛋白粘蛋白-3（TIM-3）、巯基氧化酶1（QSOX1）在妊娠合并乙型肝炎病毒（HBV）感染患者中的表达水平及与母婴不良结局的关系。方法 选取2019年10月—2023年10月锦州医科大学附属第三医院收治的103例妊娠合并HBV患者作为HBV组，另选取50例同期健康体验妊娠女性作为对照组。HBV组根据母婴结局分为良好结局组（84例）和不良结局组（19例）。比较各组临床资料及血清DNMT1、TIM-3、QSOX水平，通过多因素一般Logistic回归模型分析妊娠合并HBV感染患者母婴结局的影响因素，构建列线图并绘制受试者工作特征（ROC）曲线。结果 HBV组血清DNMT1、TIM-3、QSOX1水平均高于对照组（P <0.05）。不良结局组HBV DNA载量≥1.0×10³ IU/mL占比、TBIL、AST、ALT水平均高于良好结局组（P <0.05）。不良结局组血清DNMT1、TIM-3、QSOX1水平均高于良好结局组（P <0.05）。多因素一般Logistic回归分析结果表明：HBV DNA载量高［O^R=28.257（95% CI：2.069，385.982）］、DNMT1水平高（［O^R=1.316（95% CI：1.039，1.666）］、TIM-3水平高［O^R=2.249（95% CI：1.319，3.833）］、QSOX1水平高［O^R=1.431（95% CI：1.151，1.780）］均为妊娠合并HBV感染患者母婴不良结局的危险因素（P <0.05）。ROC曲线结果表明，血清DNMT1、TIM-3、QSOX1水平三者联合预测妊娠合并HBV感染患者母婴不良结局的曲线下面积为0.962，敏感性为94.7%（95% CI：0.740，0.999），特异性为90.6%（95% CI：0.736，0.917）。结论 血清DNMT1、TIM-3、QSOX1在妊娠合并HBV感染患者中表达升高，并对母婴不良结局具有良好的预测价值。

Abstract:

Objective To investigate the serum levels of DNA methyltransferase 1 (DNMT1), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), and quiescin sulfhydryl oxidase 1 (QSOX1) in pregnant women with hepatitis B virus (HBV) infection, and their associations with adverse maternal and neonatal outcomes.Methods One hundred and three pregnant women with HBV infection admitted to the Third Affiliated Hospital of Jinzhou Medical University between October 2019 and October 2023 were enrolled as the HBV group. Fifty healthy pregnant women undergoing routine check-ups during the same period served as the control group. The HBV group was further divided into the favorable outcome (n = 84) and adverse outcome (n = 19) subgroups based on maternal and neonatal outcomes. Clinical data and serum levels of DNMT1, TIM-3, and QSOX were compared across groups. Multivariable logistic regression analysis identified factors influencing maternal and neonatal outcomes in pregnant women with HBV infection, based on which a nomogram was constructed. Receiver operating characteristic (ROC) curves assessed the predictive values of serum levels of DNMT1, TIM-3, and QSOX for adverse maternal and neonatal outcomes.Results Serum levels of DNMT1, TIM-3, and QSOX1 were higher in the HBV group than those in the control group (P < 0.05). The adverse outcome group exhibited greater percentage of patients with higher HBV DNA load, and higher levels of TBIL, AST, and ALT than the favorable outcome group (P < 0.05). Serum DNMT1, TIM-3, and QSOX1 levels were also higher in the adverse outcome group than in the favorable outcome group (P < 0.05). Multivariable logistic regression analysis revealed that high HBV DNA load [O^R = 28.257 (95% CI: 2.069, 385.982) ], elevated DNMT1 levels [O^R = 1.316 (95% CI: 1.039, 1.666) ], elevated TIM-3 levels [O^R = 2.249 (95% CI: 1.319, 3.833) ], and elevated QSOX1 levels [O^R = 1.431 (95% CI: 1.151, 1.780) ] were risk factors for adverse maternal and neonatal outcomes in pregnant women with HBV infection (P < 0.05). ROC curve analysis revealed that the combination of serum levels of DNMT1, TIM-3, and QSOX1 for predicting adverse maternal and neonatal outcomes in pregnant women with HBV infection demonstrated an area under the curve of 0.962, with a sensitivity of 94.7% (95% CI: 0.740, 0.999) and a specificity of 90.6% (95% CI: 0.736, 0.917).Conclusion Serum levels of DNMT1, TIM-3, and QSOX1 are elevated in pregnant women with HBV infection and demonstrate good predictive value for adverse maternal and neonatal outcomes.