Epigenetic Profiles Reveal That ADCYAP1 Serves as Key Molecule in Gestational Diabetes Mellitus

Abstract

Gestational diabetes mellitus (GDM) refers to the condition which shows abnormal glucose metabolism that occurs during pregnancy, while normal glucose metabolism before pregnancy. In the present study, a novel analytical procedure was used to explore the key molecule of gestational diabetes mellitus. First, the weighted pathway model was carried out subsequently to eliminate the gene-overlapping effects among pathways. Second, we assessed the enriched pathways by a combination of Fisher’s t-test and the Mann–Whitney U test. We carried out the functional principal component analysis by estimating F values of genes to identify the hub genes in the enriched pathways. Results showed that a total of 4 differential pathways were enriched. The key pathway was considered as the insulin secretion pathway. F values of each gene in the key pathway were calculated. Three hub molecules were identified as hub differentially methylated genes, namely, CAMK2B, ADCYAP1, and KCNN2. In addition, by further comparing the gene expression data in a validation cohort, one key molecule was obtained, ADCYAP1. Therefore, ADCYAP1 may serve as a potential target for the treatment of GDM.

Epigenetic Factors in Gestational Diabetes From Mother to Child: A Narrative Review

“…Adenylyl cyclase is a key enzyme of the G-protein coupled signaling pathway that is involved with a plethora of hormones, including insulin. In a 2019 epigenetic profiling manuscript, placental samples from 82 patients were screened for differentially methylated genes and 3 molecules were identified: CAMK2B, ADCYAP1, and KCNN2 [14] In addition, a smaller scale study with 24 patients also identified CAMTA1, a transcriptional activator involved in insulin secretion and regulation to be differentially methylated. More specifically, there was decreased methylation of CAMTA1 in the peripheral blood of GDM patients compared to control; further suggesting that disruption of insulin regulation and function is partially responsible for GDM development [15].…”

Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis

“…The GDM is an extremely complicated pathophysiological process and controlled by various genes and signaling pathways. Genes such as PVT1 [10], IL-6, IL-10, and TNF-α [11], CAPN10 [12], ADCYAP1 [13] and ABHD5 [14] are associated with GDM. Signaling pathways such as PI3K/AKT signaling pathway [15], AMPK signaling pathway [16], vitamin D signaling pathways [17], TLR4/NF-kappaB Signaling Pathway [18] and AGEs-RAGE signaling pathway [19] are linked with GDM.…”