1330-P: Molecular Biomarkers during Gestational Diabetes Mellitus

Abstract

Background/Aim: Gestational diabetes mellitus (GDM) is associated with short- and long-term complication in both mothers and offspring. Molecular mechanisms are attracting increased interest for their potential as biomarkers for GDM that could lead to improved detection of GDM with positive effects on health outcomes. The aim of this study was to explore the potential of DNA methylation and single nucleotide polymorphisms (SNPs) to serve as molecular biomarkers for GDM in South African women. Methods: Genome-wide DNA methylation using a MethylationEPIC BeadChip Array (n=24) and gene-specific methylation of the adiponectin (ADIPOQ) gene using bisulfite pyrosequencing (n=286) were profiled in the peripheral blood of women with or without GDM. In addition, variants ADIPOQ rs266729 and rs17300539, and methylenetetrahydrofolate reductase (MTHFR) rs1801133 were quantified using quantitative real-time PCR (n=449). Results: Genome-wide methylation analysis identified 1046 differentially methylated CpG sites (associated with 939 genes), of which 148 CpG sites were hypermethylated and 898 CpG sites were hypomethylated (p<0.01). Among the top five CpG sites, one CpG mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which has been shown to regulate insulin production and secretion. Two CpG sites (-3410: p=0.048 and -3400: p=0.004) in the ADIPOQ promoter were hypomethylated during GDM in Human Immunodeficiency Virus (HIV) negative, but not in HIV positive women. Lastly, no association between ADIPOQ and MTHFR polymorphisms and GDM was observed in our population. Discussion: DNA methylation may offer potential as molecular biomarkers for GDM in a South African population. Future longitudinal studies in larger samples that include both HIV negative and positive pregnant women are warranted to explore the candidacy of DNA methylation as molecular biomarkers for GDM. Disclosure S. Dias: None. S. Adam: None. P. Rheeder: None. J. Louw: None. C. Pheiffer: None. Funding National Research Foundation (99391); South African Medical Research Council