Abstract
BackgroundCircular RNA (circRNA) is involved in the pathological processes of various diseases. CircRNA is more stable than linear RNAs and is expressed in high levels in tissues, making it a better biomarker candidate than linear RNAs. In this study, we aimed to identify potential circRNA biomarkers of gestational diabetes mellitus (GDM).MethodsA retrospective case–control study was conducted using data and samples from women treated at a hospital in China between July 10, 2017, and February 15, 2018. We collected serum samples from 40 healthy pregnant women (controls) and 40 women with GDM (cases) during the second trimester as well as 65 controls and 65 cases during the third trimester of pregnancy. Placenta tissues and neonatal cord blood were each from another 20 cases and 20 controls. We selected six circRNAs (hsa_circRNA_0054633, hsa_circRNA_103410, hsa_circRNA_063981, hsa_circRNA_102682, hsa_circRNA_0018508, and hsa_circRNA_406918) as candidate biomarkers and used quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to measure their concentrations in the serum and placental tissues. The Pearson correlation test was used to assess the correlation between various circRNAs and between circRNA and clinical variables. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic value of circRNAs for GDM at each stage.ResultsHsa_circRNA_0054633 was highly expressed in the blood during the second and third trimesters; its expression was also high in the placenta but low in the cord blood (P < 0.05). Hsa_cirRNA_0054633 was highly correlated with GHBA1 and GHBA1c levels in maternal blood samples at various stages of the GDM group (including placental tissue and umbilical cord blood) (P < 0.05). Hsa_circRNA_063981, hsa_circRNA_102682, and hsa_circRNA_103410 were also differentially expressed between the case and control groups at different stages (P < 0.05). There was a strong correlation between hsa_circRNA_0054633 and hsa_circRNA_103410 levels in third-trimester maternal blood (P = 0.000, r = 0.554) and in neonatal umbilical cord blood (P = 0.000, r = 0.866). Hsa_circRNA_0054633 showed a significant diagnostic value in the second and third trimesters of pregnancy, placenta, and cord blood (AUC = 0.793, 0.664, 0.747, and 0.783, respectively, P < 0.001).ConclusionThis study suggests that hsa_cirRNA_0054633 is abnormally expressed in GDM patients and may play a potential role in the development of GDM. The possibility of using circRNAs for the diagnosis of GDM requires additional investigation in future studies.
Highlights
Gestational diabetes mellitus (GDM) refers to the condition of having normal glucose metabolism before pregnancy but impaired glucose tolerance and elevated fasting glucose concentrations during pregnancy [1]
In 2013, the International Diabetes Federation (IDF) reported that an estimated 21.4 million live births were from women with GDM [5], and these newborns were prone to macrosomia, shoulder dystocia, and neonatal hypoglycemia [5, 6]
Hsa_circRNA_0054633 was highly expressed in the third trimester in the GDM group and was correlated with hsa_circRNA_103410 By quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), we found that the level of hsa_circRNA_0054633 in GDM patients was significantly higher than that in the controls in the third-trimester cohort (P = 0.002, Fig. 2)
Summary
Gestational diabetes mellitus (GDM) refers to the condition of having normal glucose metabolism before pregnancy but impaired glucose tolerance and elevated fasting glucose concentrations during pregnancy [1]. Diagnosis of GDM relies primarily on the diagnostic criteria given by the American Diabetes Association (ADA) and the International Association of Diabetes and Pregnancy Study Group (IADPSG) [7]. A standard test is performed during 24 to 28 weeks of gestation, sometimes delayed to 32 weeks Testing at this stage can often delay the diagnosis of GDM, causing serious adverse consequences for the mother and child. Some researchers have sought to find new indicators of GDM through associations between genetic variants and GDM [11, 12], but delays the diagnosis of the disease, causing adverse consequences. CircRNA is more stable than linear RNAs and is expressed in high levels in tissues, making it a better biomarker candidate than linear RNAs. In this study, we aimed to identify potential circRNA biomarkers of gestational diabetes mellitus (GDM)
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