ORIGINAL ARTICLE Methylation profile of genes involved in inflammation, in the blood from pregnancies with maternal preeclampsia due to untreated gestational diabetes mellitus Panagiotis Halvatsiotis 1 & Theodora Tsokaki 2 & Charalambos Chrelias 2 & Dimitrios Kassanos 2 & Ekaterini Domali 3 & Maria Gazouli 4 & Georgios Dimitriadis 1 & Sophia Kalantaridou 2 Received: 26 January 2019 /Accepted: 21 May 2019 /Published online: 1 June 2019 # Hellenic Endocrine Society 2019 Abstract Purpose To investigate DNA methylation changes in peripheral blood from patients with gestational diabetes mellitus (GDM) and preeclampsia (PE) due to poorly treated GDM. Methods Eighteen pregnant women participated in the study: 6 with GDM, 6 with PE, and 6 healthy controls. The promoter methylation status of genes was profiled using the Human Inflammatory Response and Autoimmunity EpiTect Methyl II Signature PCR Array profiles. The results were validated with quantitative real-time polymerase chain reaction (qRT-PCR). Results Fewer inflammation-related genes were significantly hypomethylated in PE cases compared to healthy subjects than in GDM cases. Some of the examined genes show different methylation patterns between GDM and PE. Conclusions The epigenetic changes observed in this study indicate that GDM and PE exhibit specific DNA methylation profiles, with possible clinical applications. Keywords Gestational diabetes mellitus . Preeclampsia . Methylation . Inflammation . Diagnosis . Prognosis Introduction Gestational diabetes mellitus (GDM) is a state of glucose in- tolerance with onset or first recognition during pregnancy [1]. GDM, when poorly treated, increases the risk of adverse preg- nancy outcomes, such as preeclampsia (PE), a multisystem disorder characterized by new onset of hypertension and pro- teinuria or end-organ dysfunction [2, 3]. Although most af- fected pregnancies proceed to term or near term with good maternal and fetal outcomes, these pregnancies are neverthe- less at increased risk for maternal and/or fetal mortality or serious morbidity [4, 5]. The incidences of hypertension and PE are increased in pregnant women with diabetes [6]. However, it has been observed that insulin resistance appears to augment the risk of developing PE [7, 8], while impaired endothelium-dependent vasodilation seems to be related to the duration of diabetes [9]. Hence, insulin resistance is the main component in the path- ophysiology of PE, with enough evidence suggesting inflam- mation as the central feature. Overexpression of this inflamma- tory response leads to vascular disease which is the basis in immunobiology of PE [10]. Additionally, many investigators [11, 12] have pointed to the role of the maternal immune sys- tem in the pathogenesis of PE. Proinflammatory cytokines, neutrophil activation, and endothelial dysfunction are related to the pathophysiology of PE [13]. Perez-Sepulveda et al. [14] reported that Th1/Th2/Th17 and regulatory T cells and the dendritic cells could play a basic role in PE pathogenesis. Given the numerous processes through which methylation plays a part in the development of this condition, researchers have also linked DNA methylation errors to a number of sig- nificant consequences, including several diseases. Regarding * Maria Gazouli mgazouli@med.uoa.gr 1 2nd Department of Int. Med Propaedeutic BAttikon^ University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece 2 3rd Department of Obstetrics and Gynecology, BAttikon^ University Hospital, Athens, Greece 3 1st Department of Obstetrics & Gynecology, BAlexandra^ Hospital, University of Athens, Medical School, Athens, Greece 4 Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Michalakopoulou 176, 11527 Athens, Greece Hormones (2019) 18:173–178 https://doi.org/10.1007/s42000-019-00111-x