Coban U, Celik Z B
Department of Gynecology and Obstetrics, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey.
Eur Rev Med Pharmacol Sci. 2023 Feb;27(3):1051-1057. doi: 10.26355/eurrev_202302_31201.
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).
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).
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).
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.
妊娠期糖尿病（GDM）的特征是新发葡萄糖不耐受，在妊娠中期和晚期最为常见。表观遗传修饰调节葡萄糖及其与代谢途径的细胞相互作用。新出现的证据表明，表观遗传变化促成了GDM的病理生理学。由于这些患者血糖水平较高，胎儿和母亲的代谢谱会影响这些表观遗传变化。因此，我们旨在研究三种基因启动子的甲基化谱的潜在改变：自身免疫调节因子（AIRE）基因、基质金属蛋白酶-3（MMP-3）和钙电压门控通道亚基α1 G（CACNA1G）。
本研究共纳入44例诊断为GDM的患者和20例对照。从所有患者的外周血样本中进行DNA分离和亚硫酸氢盐修饰。然后，通过甲基化特异性聚合酶链反应（PCR）甲基化特异性（MSP）确定AIRE、MMP-3和CACNA1G基因的启动子甲基化状态。
我们的结果表明，与健康孕妇相比，GDM患者中AIRE和MMP-3的甲基化状态变为未甲基化（p<0.001）。然而，CACNA1G启动子甲基化状态在实验组之间未显示出显著变化（p>0.05）。
我们的结果表明，AIRE和MMP-3是受表观遗传修饰影响的基因，这可能是母婴健康长期代谢影响的原因之一，并且在未来研究中可能成为GDM预防、诊断或治疗的靶点。
