title: An epigenomic signature of postprandial hyperglycemia in peripheral blood leukocytes.
abstract: Postprandial hyperglycemia is known to be one of the earliest signs of abnormal glucose homeostasis associated with type 2 diabetes. This study aimed to assess clinical significance of a 1-h postprandial glucose level for the development of diabetes, and identify epigenetic biomarkers of postprandial hyperglycemia. We analyzed clinical data from the oral glucose tolerance tests for healthy subjects (n=4502). The ratio (Glu60/Glu0) of 1-h glucose levels to fasting glucose levels was significantly associated with an insulin sensitive index (QUICKI, quantitative insulin sensitivity check index) (β=0.055, P=1.25E-04) as well as a risk of future pre-diabetic and diabetic conversion. Next, DNA methylation profile analyses of 24 matched pairs of the high and low Glu60/Glu0 ratio subjects showed that specific DNA methylation levels in the promoter region of an olfactory receptor gene (olfactory receptor gene family10 member A4, OR10A4) were associated with the Glu60/Glu0 ratios (β=0.337, P=0.03). Moreover, acute oral glucose challenges decreased the DNA methylation levels of OR10A4 but not the global DNA methylation in peripheral leukocytes of healthy subjects (n=7), indicating that OR10A4 is a specific epigenomic target of postprandial hyperglycemia. This work suggests possible relevance of olfactory receptor genes to an earlier molecular biomarker of peripheral hyperglycemia and diabetic conversion.
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Osong, Korea.
authors.forename: Sung-Mi
authors.initials: SM
authors.lastname: Shim
authors.affiliation: National Biobank of Korea, Center for Genome Science, Korea Centers for Disease Control and Prevention, Osong, Korea.
authors.forename: Yoon-Kyung
authors.initials: YK
authors.lastname: Cho
authors.affiliation: National Biobank of Korea, Center for Genome Science, Korea Centers for Disease Control and Prevention, Osong, Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Hong
authors.affiliation: National Biobank of Korea, Center for Genome Science, Korea Centers for Disease Control and Prevention, Osong, Korea.
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Osong, Korea.
authors.forename: Jae-Pil
authors.initials: JP
authors.lastname: Jeon
mesh_terms: D001786:Blood Glucose / Q000032:analysis*; D019175:DNA Methylation; D057890:Epigenomics; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism*; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose