Differential Methylation in Promoter Regions of the Genes NR3C1 and HSP90AA1, Involved in the Regulation, and Bioavailability of Cortisol in Leukocytes of Women With Preeclampsia

Introduction:Hypertensive disorders are of interest in obstetrics and gynecology because they are the second place among causes of maternal mortality and a source of complications in the short, mid, and long term. Even if the pathophysiological process behind preeclampsia (PE) is still unknown, stress factors have been revealed to play an important role in the genesis of this pathologic process. Methods:A case-control study was designed with the purpose of determining if there is a differential methylation inNR3C1, HSD11B2, CYP11A1, CRHBP, TEAD3, andHSP90AA1genes, related to signaling of the hypothalamic-pituitary-adrenal axis, and its regulation on early-onset PE (EOPE). Results:A total of 20 cases and 20 controls were studied by DNA methylation analysis, demonstrating differences among groups in the percentage of methylation of theNR3C1gene. After a contingency analysis, an odds ratio (OR) for PE of 12.25 was identified forNR3C1and 9.9 forHSP90AA1genes. NR3C1, TEAD3, andHSP90AA1genes showed a positive correlation with the systolic and diastolic blood pressure levels with ap <= 0.05. Conclusion:This study found a differential methylation in the glucocorticoid receptor (GR)NR3C1and its co-chaperoneHSP90AA1in women with PE, with a possible regulatory role in the response to stress in pregnancy and is a likely physiopathological mechanism in PE.