Journal
EPIGENETICS
Volume 11, Issue 7, Pages 482-488Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15592294.2016.1178418
Keywords
ABCG1; adipose tissue; blood; DNA methylation; epigenetics; liver; pancreatic islets; PHOSPHO1; skeletal muscle; type 2 diabetes
Funding
- Sigrid Juselius Foundation
- Folkhalsan Research Foundation
- Nordic Center of Excellence in Disease Genetics
- Finnish Diabetes Research Foundation
- Finnish Medical Society
- Helsinki University Central Hospital Research Foundation
- Perklen Foundation
- Ollqvist Foundation
- Narpes Health Care Foundation
- Ahokas Foundation
- Health Care Center in Vasa
- Health Care Center in Narpes
- Health Care Center in Korsholm
- Swedish Research Council [521-2010-2745, 523-2010-1061]
- Region Skane (ALF)
- Knut and Alice Wallenberg Foundation [2009-]
- Novo Nordisk Foundation
- EFSD/Lilly Fellowship
- Soderberg Foundation
- Royal Physiographic Society in Lund
- Sigurd och Elsa Goljes Minne
- Swedish Diabetes foundation
- Pahlsson Foundation
- EXODIAB
- Linne grant [B31 5631/2006]
- Academy of Finland [120979, 138006, 131593]
- Finnish Cultural Foundation
- Kuopio University Hospital EVO and VTR funding
- Swedish Medical Research Council [K2008-55X-15358-04-3]
- Danish Council for Strategic Research
- Danish Council for Independent Research
- Linnaeus grant (LUDC) [349-2008-6589]
- strategic research area grant (EXODIAB [Excellence Of Diabetes Research in Sweden]) [2009-1039]
- Lundberg Foundation [359]
- Avtal om Lakarutbildning och Forskning
- Tore Nilsson Foundation
- Syskonen Svensson Foundation
- Diabetes Foundation
- Kungliga Fysiografiska Sallskapet i Lund
- European Foundation for the Study of Diabetes/Lilly Foundation
- Swedish Department of Higher Education
- Danish National Research Foundation [DNRF55]
- TrygFonden
- Novo Nordisk Fonden [NNF14OC0010995] Funding Source: researchfish
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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.
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