Khadir Fatemeh, Rahimi Zohreh, Vaisi-Raygani Asad, Shakiba Ebrahim, Naseri Rozita
Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Rep Biochem Mol Biol. 2022 Oct;11(3):493-501. doi: 10.52547/rbmb.11.3.493.
Preeclampsia is a multifactorial hypertensive disorder of pregnancy with multisystem involvement. Recent studies have demonstrated that preeclampsia is associated with increased placental oxidative stress at the cellular level. The nuclear factor erythroid-2-like 2 (Nrf2) / Kelch-like ECH-associated protein 1 (Keap1) signaling is an antioxidant pathway that plays an important role in protecting cells against oxidative stress. Here, we aimed to determine the possible association between the Keap1 variants and genetic susceptibility to preeclampsia.
In a case-control study, 150 preeclampsia patients and 150 women with normal pregnancy from Northern Iran were selected to evaluate the genotypes of Keap1 (rs11085735) using the polymerase chain reaction (PCR)-restriction length polymorphism (RFLP) method.
A significant association between genotypes of Keap1 rs11085735 polymorphism with the renal function biomarkers and the risk of preeclampsia was not found. However, the aspartate aminotransferase (AST) level was higher in the presence of the Keap1 AA genotype compared to AC and CC genotypes. We found a significantly higher prevalence of gestational diabetes mellitus (GDM) in mild- and severe- preeclampsia and also hypothyroidism in severe preeclampsia compared to controls.
We found an association between preeclampsia with GDM and hypothyroidism. Our findings suggest that the Keap1rs11085735 polymorphism may not be a risk factor for susceptibility to preeclampsia in our studied population; however, this polymorphism could affect the activity of AST.
子痫前期是一种多因素导致的妊娠高血压疾病，涉及多系统。近期研究表明，子痫前期在细胞水平上与胎盘氧化应激增加有关。核因子红细胞2样2（Nrf2）/ Kelch样ECH相关蛋白1（Keap1）信号通路是一种抗氧化途径，在保护细胞免受氧化应激方面发挥重要作用。在此，我们旨在确定Keap1基因变异与子痫前期遗传易感性之间的可能关联。
在一项病例对照研究中，选取了150例来自伊朗北部的子痫前期患者和150例正常妊娠女性，采用聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）方法评估Keap1（rs11085735）的基因型。
未发现Keap1 rs11085735多态性的基因型与肾功能生物标志物及子痫前期风险之间存在显著关联。然而，与AC和CC基因型相比，Keap1 AA基因型存在时天冬氨酸转氨酶（AST）水平更高。我们发现，与对照组相比，轻度和重度子痫前期患者中妊娠期糖尿病（GDM）的患病率显著更高，重度子痫前期患者中甲状腺功能减退的患病率也显著更高。
我们发现子痫前期与GDM和甲状腺功能减退之间存在关联。我们的研究结果表明，在我们的研究人群中，Keap1rs11085735多态性可能不是子痫前期易感性的危险因素；然而，这种多态性可能会影响AST的活性。
