Gestational Diabetes Mellitus (GDM), Hypothyroidism, and Gene Variants (Keap۱ Rs۱۱۰۸۵۷۳۵) in Patients with Preeclampsia

Background: 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‑۲‑like ۲ (Nrf۲) / Kelch‑like ECH‑associated protein ۱ (Keap۱) 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 Keap۱ variants and genetic susceptibility to preeclampsia. Methods: In a case-control study, ۱۵۰ preeclampsia patients and ۱۵۰ women with normal pregnancy from Northern Iran were selected to evaluate the genotypes of Keap۱ (rs۱۱۰۸۵۷۳۵) using the polymerase chain reaction (PCR)-restriction length polymorphism (RFLP) method. Results: A significant association between genotypes of Keap۱ rs۱۱۰۸۵۷۳۵ 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 Keap۱ 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. Conclusions: We found an association between preeclampsia with GDM and hypothyroidism. Our findings suggest that the Keap۱rs۱۱۰۸۵۷۳۵ polymorphism may not be a risk factor for susceptibility to preeclampsia in our studied population; however, this polymorphism could affect the activity of AST.

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Keywords: Gestational diabetes mellitus ، Hypothyroidism ، Keap۱ variants ، Oxidative stress ، Preeclampsia.