Department of Biochemistry, Konya Training and Research Hospital, Konya, Turkey.
Department of Perinatology, Konya Training and Research Hospital, Konya, Turkey.
J Obstet Gynaecol. 2021 Aug;41(6):904-909. doi: 10.1080/01443615.2020.1820463. Epub 2020 Nov 24.
Our aim was to investigate serum zonulin levels in intrahepatic cholestasis of pregnancy (ICP) and to determine the usefulness of zonulin in ICP follow-up. A prospective case-control study was carried out which included 88 pregnant women (44 patients with ICP and 44 controls). Maternal serum samples obtained from all participants and zonulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Compared with controls, women with ICP had significantly higher zonulin levels (mean 0.728 ± 0.520 ng/mL vs. 1.303 ± 0.63 ng/mL, 001). According to the receiver operating characteristic (ROC) analysis performed for the predictive value of zonulin levels for ICP, the area under the curve (AUC) was 0.761 (95% CI: 0.661-0.860). Multivariable logistic regression analysis revealed serum zonulin levels was independently associated with adverse perinatal outcomes (OR = 1.278, 95% CI: 0.232-7.041), severity ICP (OR: 7.535, 95% CI: 1.597-13.553) and also unresponsiveness to treatment in ICP (OR: 4.178, 95% CI: 0.929-8.784).IMPACT STATEMENT Zonulin is a regulator protein that increases the intestinal permeability by modulating the intercellular tight junctions (TJ). It is the only physiological protein known to control intestinal permeability and damage of the intestinal barrier is one of the causes of absorption disorders, inflammation and autoimmunity. ICP is a relatively non-threatening condition to women but is linked with a higher risk of preterm delivery, foetal distress and foetal death. This study showed that increased levels of zonulin are associated with adverse perinatal outcomes, severity of ICP and unresponsiveness to treatment in ICP. Focussing on preservation of intestinal permeability may be an alternative preventive strategy to reduce the adverse perinatal outcomes and severity of ICP. Further longitudinal studies are needed to verify the relationships among zonulin levels and pregnancy-related diseases.
我们的目的是研究妊娠期肝内胆汁淤积症（ICP）患者血清中肠通透素（zonulin）的水平，并确定 zonulin 在 ICP 随访中的应用价值。本研究为前瞻性病例对照研究，共纳入 88 名孕妇（44 例 ICP 患者和 44 例对照组）。采用酶联免疫吸附法（ELISA）检测所有参与者的血清样本，以确定 zonulin 水平。与对照组相比，ICP 患者的 zonulin 水平显著更高（平均 0.728±0.520ng/mL 比 1.303±0.63ng/mL，P=0.001）。根据 ROC 分析 zonulin 水平对 ICP 的预测价值，曲线下面积（AUC）为 0.761（95%CI：0.661-0.860）。多变量 logistic 回归分析显示，血清 zonulin 水平与不良围生期结局（OR=1.278，95%CI：0.232-7.041）、ICP 严重程度（OR：7.535，95%CI：1.597-13.553）和 ICP 治疗反应不良（OR：4.178，95%CI：0.929-8.784）独立相关。
肠通透素（zonulin）是一种调节蛋白，通过调节细胞间紧密连接（TJ）增加肠道通透性。它是唯一已知能控制肠道通透性的生理性蛋白，而肠道屏障的损伤是吸收障碍、炎症和自身免疫的原因之一。ICP 对女性来说相对没有威胁，但与早产、胎儿窘迫和胎儿死亡的风险增加有关。本研究表明，zonulin 水平升高与不良围生期结局、ICP 严重程度和 ICP 治疗反应不良相关。关注肠道通透性的维持可能是降低不良围生期结局和 ICP 严重程度的一种替代预防策略。需要进一步的纵向研究来验证 zonulin 水平与妊娠相关疾病之间的关系。
