title: Maternal genome-wide DNA methylation profiling in gestational diabetes shows distinctive disease-associated changes relative to matched healthy pregnancies.
abstract: Several recent reports have described associations between gestational diabetes (GDM) and changes to the epigenomic landscape where the DNA samples were derived from either cord or placental sources. We employed genome-wide 450K array analysis to determine changes to the epigenome in a unique cohort of maternal blood DNA from 11 pregnant women prior to GDM development relative to matched controls. Hierarchical clustering segregated the samples into 2 distinct clusters comprising GDM and healthy pregnancies. Screening identified 100 CpGs with a mean β-value difference of ≥0.2 between cases and controls. Using stringent criteria, 5 CpGs (within COPS8, PIK3R5, HAAO, CCDC124, and C5orf34 genes) demonstrated potentials to be clinical biomarkers as revealed by differential methylation in 8 of 11 women who developed GDM relative to matched controls. We identified, for the first time, maternal methylation changes prior to the onset of GDM that may prove useful as biomarkers for early therapeutic intervention.
authors.affiliation: a Institute for Science and Technology in Medicine , Keele University, Guy Hilton Research Center , Staffordshire , UK.|b Academic Unit of Obstetrics and Gynecology, University Hospital of North Midlands NHS Trust , Stoke-on-Trent, Staffordshire , UK.
authors.forename: Pensee
authors.identifier: 0000-0003-0011-5636
authors.initials: P
authors.lastname: Wu
authors.affiliation: a Institute for Science and Technology in Medicine , Keele University, Guy Hilton Research Center , Staffordshire , UK.
authors.forename: William E
authors.identifier: 0000-0002-9280-5484
authors.initials: WE
authors.lastname: Farrell
authors.affiliation: a Institute for Science and Technology in Medicine , Keele University, Guy Hilton Research Center , Staffordshire , UK.
authors.forename: Kim E
authors.identifier: 0000-0002-9460-4424
authors.initials: KE
authors.lastname: Haworth
authors.affiliation: c School of Veterinary Medicine and Science, University of Nottingham , Leicestershire , UK.|d Advanced Data Analysis Center , University of Nottingham , Leicestershire , UK.
authors.forename: Richard D
authors.identifier: 0000-0001-6855-5481
authors.initials: RD
authors.lastname: Emes
authors.affiliation: a Institute for Science and Technology in Medicine , Keele University, Guy Hilton Research Center , Staffordshire , UK.
authors.forename: Mark O
authors.identifier: 0000-0002-1124-2940
authors.initials: MO
authors.lastname: Kitchen
authors.affiliation: a Institute for Science and Technology in Medicine , Keele University, Guy Hilton Research Center , Staffordshire , UK.|e Haywood Rheumatology Center, Haywood Hospital , Staffordshire , UK.
authors.forename: John R
authors.identifier: 0000-0002-7969-1363
authors.initials: JR
authors.lastname: Glossop
authors.affiliation: f Department of Diabetes and Endocrinology , University Hospital of North Midlands NHS Trust , Stoke-on-Trent, Staffordshire , UK.
authors.forename: Fahmy W
authors.identifier: 0000-0002-6986-7417
authors.initials: FW
authors.lastname: Hanna
authors.affiliation: a Institute for Science and Technology in Medicine , Keele University, Guy Hilton Research Center , Staffordshire , UK.
authors.forename: Anthony A
authors.identifier: 0000-0001-8678-0404
authors.initials: AA
authors.lastname: Fryer
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D016640:Diabetes, Gestational / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D011247:Pregnancy
keywords: 450K array; biomarker; epigenetics; fetal programming; gestational diabetes