Study on the relationship between DNA methylation of target CpG sites in peripheral blood and gestational diabetes during early pregnancy.

Genome-wide DNA methylation profiling have been used to find maternal CpG sites related to the occurrence of gestational diabetes mellitus (GDM). However, none of these differential sites found has been verified in a larger sample. Here, our aim was to evaluate whether first trimester changes in target CpG sites in the peripheral blood of pregnancy women predict subsequent development of GDM. This nested case-control study was based upon an early pregnancy follow-up cohort (ChiCTR1900020652). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites of 80 GDM cases and 80 matched healthy controls during the early pregnancy (10-15 weeks) were assessed using MethylTarget sequencing. The best cut-off level for methylation of CpG site was determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at another 6 CpG sites were significantly lower (FDR < 0.05). The area under the ROC curve at each methylation level of the significant CpG sites ranged between 0.593 and 0.650 for the occurrence of GDM. After adjusting for possible confounders, the hypermethylation status of CpG site 68167324 (OR = 3.168, 1.038-9.666) and 24837915 (OR = 5.232, 1.659-16.506) was identified as more strongly associated with GDM; meanwhile, the hypermethylation of CpG site 157130156 (OR = 0.361, 0.135-0.966) and 89438648 (OR = 0.206, 0.065-0.655) might indicate lower risk of GDM. The methylation status of target CpG sites in the peripheral blood of pregnant women during the first trimester may be associated with GDM pathogenesis, and has potential as a predictor of GDM.