Gestational Diabetes Mellitus (GDM), Hypothyroidism, and Gene Variants (Keap1 Rs11085735) in Patients with Preeclampsia

Abstract

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-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. Methods: 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. Results: 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. Conclusions: 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