title: Genome-Wide DNA Methylation in Mixed Ancestry Individuals with Diabetes and Prediabetes from South Africa.
abstract: Aims. To conduct a genome-wide DNA methylation in individuals with type 2 diabetes, individuals with prediabetes, and control mixed ancestry individuals from South Africa. Methods. We used peripheral blood to perform genome-wide DNA methylation analysis in 3 individuals with screen detected diabetes, 3 individuals with prediabetes, and 3 individuals with normoglycaemia from the Bellville South Community, Cape Town, South Africa, who were age-, gender-, body mass index-, and duration of residency-matched. Methylated DNA immunoprecipitation (MeDIP) was performed by Arraystar Inc. (Rockville, MD, USA). Results. Hypermethylated DMRs were 1160 (81.97%) and 124 (43.20%), respectively, in individuals with diabetes and prediabetes when both were compared to subjects with normoglycaemia. Our data shows that genes related to the immune system, signal transduction, glucose transport, and pancreas development have altered DNA methylation in subjects with prediabetes and diabetes. Pathway analysis based on the functional analysis mapping of genes to KEGG pathways suggested that the linoleic acid metabolism and arachidonic acid metabolism pathways are hypomethylated in prediabetes and diabetes. Conclusions. Our study suggests that epigenetic changes are likely to be an early process that occurs before the onset of overt diabetes. Detailed analysis of DMRs that shows gradual methylation differences from control versus prediabetes to prediabetes versus diabetes in a larger sample size is required to confirm these findings.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town 7535, South Africa.
authors.forename: Tandi E
authors.identifier: 0000-0001-7291-714X
authors.initials: TE
authors.lastname: Matsha
authors.affiliation: Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town 7505, South Africa.
authors.forename: Carmen
authors.initials: C
authors.lastname: Pheiffer
authors.affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Institute of Cardiovascular Science, The Rayne Building, University College London, London WC1E 6JF, UK.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Humphries
authors.affiliation: South African National Bioinformatics Institute, University of the Western Cape, Cape Town 7535, South Africa.
authors.forename: Junaid
authors.initials: J
authors.lastname: Gamieldien
authors.affiliation: Division of Chemical Pathology and National Health Laboratory Service (NHLS), Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town 7505, South Africa.
authors.forename: Rajiv T
authors.initials: RT
authors.lastname: Erasmus
authors.affiliation: Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town 7505, South Africa; Department of Medicine, University of Cape Town, Cape Town 8000, South Africa.
authors.forename: Andre P
authors.identifier: 0000-0002-5183-131X
authors.initials: AP
authors.lastname: Kengne