Increasing evidence implicate altered DNA methylation in the pathophysiology of
gestational diabetes mellitus (GDM). This exploratory study probed the association between GDM
and peripheral blood DNA methylation patterns in South African women. Genome-wide DNA
methylation profiling was conducted in women with (n = 12) or without (n = 12) GDM using the
Illumina Infinium HumanMethylationEPIC BeadChip array. Functional analysis of di erentially
methylated genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes
and Genomes (KEGG) pathway analyses. A total of 1046 CpG sites (associated with 939 genes)
were di erentially methylated between GDM and non-GDM groups. Enriched pathways included
GDM-related pathways such as insulin resistance, glucose metabolism and inflammation. DNA
methylation of the top five CpG loci showed distinct methylation patterns in GDM and non-GDM
groups and was correlated with glucose concentrations. Of these, one CpG site mapped to the
calmodulin-binding transcription activator 1 (CAMTA1) gene, which have been shown to regulate
insulin production and secretion and may o er potential as an epigenetic biomarker in our population.
Further validation using pyrosequencing and conducting longitudinal studies in large sample sizes
and in di erent populations are required to investigate their candidacy as biomarkers of GDM.
Supplementary Material : Table S1. Genome-wide DNA methylation profiling identified 1098 differentially methylated CpG loci.
Table S2. Differentially methylated CpG sites annotated to 942 unique genes.
Table S3. Functional enrichment analysis identified 247 KEGG pathways.
Table S4. Statistically significant KEGG pathways associated with GDM.
Table S5. GO terms enriched by differentially methylated genes, categorized into 1181 biological processes, 161 molecular functions and 99 cellular components.