title: DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk.
abstract: Identification of subjects with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention of the disease. Consequently, it is essential to search for new biomarkers that can improve the prediction of T2D. The aim of this study was to examine whether 5 DNA methylation loci in blood DNA (ABCG1, PHOSPHO1, SOCS3, SREBF1, and TXNIP), recently reported to be associated with T2D, might predict future T2D in subjects from the Botnia prospective study. We also tested if these CpG sites exhibit altered DNA methylation in human pancreatic islets, liver, adipose tissue, and skeletal muscle from diabetic vs. non-diabetic subjects. DNA methylation at the ABCG1 locus cg06500161 in blood DNA was associated with an increased risk for future T2D (OR = 1.09, 95% CI = 1.02-1.16, P-value = 0.007, Q-value = 0.018), while DNA methylation at the PHOSPHO1 locus cg02650017 in blood DNA was associated with a decreased risk for future T2D (OR = 0.85, 95% CI = 0.75-0.95, P-value = 0.006, Q-value = 0.018) after adjustment for age, gender, fasting glucose, and family relation. Furthermore, the level of DNA methylation at the ABCG1 locus cg06500161 in blood DNA correlated positively with BMI, HbA1c, fasting insulin, and triglyceride levels, and was increased in adipose tissue and blood from the diabetic twin among monozygotic twin pairs discordant for T2D. DNA methylation at the PHOSPHO1 locus cg02650017 in blood correlated positively with HDL levels, and was decreased in skeletal muscle from diabetic vs. non-diabetic monozygotic twins. DNA methylation of cg18181703 (SOCS3), cg11024682 (SREBF1), and cg19693031 (TXNIP) was not associated with future T2D risk in subjects from the Botnia prospective study.
authors.affiliation: a Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Center , Malmö , Sweden.
authors.forename: Tasnim
authors.initials: T
authors.lastname: Dayeh
authors.affiliation: b Endocrinology, Abdominal Center, Helsinki University Hospital , Helsinki , Finland.|c Folkhälsan Research Center , Helsinki , Finland.|d Diabetes and Obesity Research Program, Research Programs Unit, University of Helsinki , Finland.|e Finnish Institute for Molecular Medicine, University of Helsinki , Helsinki , Finland.
authors.forename: Tiinamaija
authors.initials: T
authors.lastname: Tuomi
authors.affiliation: f Diabetes and Endocrinology, Department of Clinical Sciences, Lund University Diabetes Center , Malmö , Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.affiliation: a Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Center , Malmö , Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Perfilyev
authors.affiliation: g Wallenberg Laboratory, Sahlgrenska University Hospital , Gothenburg , Sweden.
authors.forename: Per-Anders
authors.initials: PA
authors.lastname: Jansson
authors.affiliation: h Department of Clinical Nutrition , Institute of Public Health and Clinical Nutrition, University of Eastern Finland , Kuopio , Finland.
authors.forename: Vanessa D
authors.initials: VD
authors.lastname: de Mello
authors.affiliation: h Department of Clinical Nutrition , Institute of Public Health and Clinical Nutrition, University of Eastern Finland , Kuopio , Finland.|i Clinical Nutrition and Obesity Center, Kuopio University Hospital , Kuopio , Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.affiliation: j Department of Endocrinology , Diabetes and Metabolism , Rigshospitalet , Copenhagen , Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
authors.affiliation: f Diabetes and Endocrinology, Department of Clinical Sciences, Lund University Diabetes Center , Malmö , Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.affiliation: a Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Center , Malmö , Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Nilsson
authors.affiliation: a Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Center , Malmö , Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 / Q000235:genetics*; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004247:DNA / Q000097:blood; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics
chemical_list: C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D015415:Biomarkers; D004247:DNA; C497128:PHOSPHO1 protein, human; D010744:Phosphoric Monoester Hydrolases
keywords: ABCG1; DNA methylation; PHOSPHO1; adipose tissue; blood; epigenetics; liver; pancreatic islets; skeletal muscle; type 2 diabetes