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PLoS One. 2016 Mar 28;11(3):e0152314. doi: 10.1371/journal.pone.0152314. eCollection 2016.

Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study.

Author information

1
Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.
2
Institute of Epidemiology II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.
3
German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Germany.
4
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Duesseldorf, Germany.
5
Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Duesseldorf, Germany.
6
Institute of Human Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.
7
Institute of Human Genetics, Technische Universitaet Muenchen, Munich, Germany.
8
Hannover Unified Biobank, Hannover Medical School, Hanover, Germany.
9
Institute of Human Genetics, Hannover Medical School, Hanover, Germany.
10
Department of Endocrinology and Diabetology, University Hospital Duesseldorf, Duesseldorf, Germany.

Abstract

Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in the Region of Augsburg F4 study using the Illumina HumanMethylation 450 BeadChip. We identified a total of 31 CpG sites where methylation level was associated with measures of glucose metabolism after adjustment for age, sex, smoking, and estimated white blood cell proportions and correction for multiple testing using the Benjamini-Hochberg (B-H) method (four for fasting glucose, seven for fasting insulin, 25 for homeostasis model assessment-insulin resistance [HOMA-IR]; B-H-adjusted p-values between 9.2x10(-5) and 0.047). In addition, DNA methylation at cg06500161 (annotated to ABCG1) was associated with all the aforementioned phenotypes and 2-hour glucose (B-H-adjusted p-values between 9.2x10(-5) and 3.0x10(-3)). Methylation status of additional three CpG sites showed an association with fasting insulin only after additional adjustment for body mass index (BMI) (B-H-adjusted p-values = 0.047). Overall, effect strengths were reduced by around 30% after additional adjustment for BMI, suggesting that this variable has an influence on the investigated phenotypes. Furthermore, we found significant associations between methylation status of 21 of the aforementioned CpG sites and 2-hour insulin in a subset of samples with seven significant associations persisting after additional adjustment for BMI. In a subset of 533 participants, methylation of the CpG site cg06500161 (ABCG1) was inversely associated with ABCG1 gene expression (B-H-adjusted p-value = 1.5x10(-9)). Additionally, we observed an enrichment of the top 1,000 CpG sites for diabetes-related canonical pathways using Ingenuity Pathway Analysis. In conclusion, our study indicates that DNA methylation and diabetes-related traits are associated and that these associations are partially BMI-dependent. Furthermore, the interaction of ABCG1 with glucose metabolism is modulated by epigenetic processes.

PMID:
27019061
PMCID:
PMC4809492
DOI:
10.1371/journal.pone.0152314
[Indexed for MEDLINE]
Free PMC Article

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