The Promoter Methylations of the Autoimmune Regulator (AIRE) Gene and Matrix Metalloproteinase-3 (MMP-3) Gene May Have a Role in Gestational Diabetes Mellitus

Abstract

Objective: Gestational diabetes mellitus (GDM) is characterized by new-onset glucose intolerance and is most common in the second and third trimesters of pregnancy. Epigenetic modifications regulate glucose and its cellular interactions with metabolic pathways. Emerging evidence suggests that epigenetic changes contribute to the pathophysiology of GDM. Since these patients have high glucose levels, the metabolic profiles of the fetus and the mother can affect these epigenetic changes. Therefore, we aimed to examine the potential alterations in the methylation profiles of three gene promoters: the autoimmune regulator (AIRE) gene, matrix metalloproteinase-3 (MMP-3), and calcium voltage-gated channel subunit alpha1 G (CACNA1G). Patients and methods: A total of 44 patients diagnosed with GDM and 20 controls were involved in the study. DNA isolation and bisulfite modification were performed from peripheral blood samples of all patients. Then, the promoter methylation status of the AIRE, MMP-3, and CACNA1G genes was determined by methylation-specific polymerase chain reaction (PCR) methylation-specific (MSP). Results: Our results demonstrated that the methylation status of AIRE and MMP-3 changed to unmethylated in the GDM patients compared to healthy pregnant women (p < 0.001). However, CACNA1G promoter methylation status failed to show a significant change between experimental groups (p > 0.05). Conclusions: Our results indicated that AIRE and MMP-3 are the genes affected by epigenetic modification, which could be one of the causes of the long-term metabolic effects in maternal and fetal health and can be a target for prevention, diagnosis, or treatment for GDM in future studies.