Hyperglycemia affects global 5-methylcytosine and 5-hydroxymethylcytosine in blood genomic DNA through upregulation of SIRT6 and TETs.
5-Methylcytosine
/ analogs & derivatives
Aged
Animals
Case-Control Studies
DNA-Binding Proteins
/ genetics
Diabetes Mellitus, Experimental
/ genetics
Diabetes Mellitus, Type 2
/ genetics
Dioxygenases
/ genetics
Female
Gene Expression Regulation
Humans
Leukocytes
/ chemistry
Male
Middle Aged
Proto-Oncogene Proteins
/ genetics
Rats
Sirtuins
/ genetics
Up-Regulation
5-hydroxymethylcytosine
5-methylcytosine
SIRT6
TET
Type 2 diabetes mellitus
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
15 04 2019
15 04 2019
Historique:
received:
14
10
2018
accepted:
31
03
2019
entrez:
17
4
2019
pubmed:
17
4
2019
medline:
22
1
2020
Statut:
epublish
Résumé
Accumulating evidence suggests that epigenetic changes play key roles in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the dynamic regulation of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in diabetic peripheral blood DNA remains to be elucidated. We collected fasting blood samples (104 patients and 108 healthy controls) and glucose-stimulated blood samples at different time points (11 patients and 5 healthy controls underwent oral glucose tolerance test (OGTT)), as well as blood samples from six couples of diabetic and control rats. A HPLC-MS/MS system was used for quantifying global 5mC and 5hmC in genomic DNA from white blood cells (WBCs), and qPCR was performed for detecting mRNA expression of SIRT6 and TETs. We found that global 5mC decreased, while global 5hmC increased in both patients and diabetic rats, with lower 5mC being a risk factor of T2DM (OR = 0.524, 95%CI 0.402-0.683, p = 1.64 × 10 Hyperglycemia appeared to promote the mRNA expression of SIRT6 and TETs, which in turn might cause the dynamic changes of 5mC and 5hmC in WBCs from T2DM patients.
Sections du résumé
BACKGROUND
Accumulating evidence suggests that epigenetic changes play key roles in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the dynamic regulation of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in diabetic peripheral blood DNA remains to be elucidated.
RESULTS
We collected fasting blood samples (104 patients and 108 healthy controls) and glucose-stimulated blood samples at different time points (11 patients and 5 healthy controls underwent oral glucose tolerance test (OGTT)), as well as blood samples from six couples of diabetic and control rats. A HPLC-MS/MS system was used for quantifying global 5mC and 5hmC in genomic DNA from white blood cells (WBCs), and qPCR was performed for detecting mRNA expression of SIRT6 and TETs. We found that global 5mC decreased, while global 5hmC increased in both patients and diabetic rats, with lower 5mC being a risk factor of T2DM (OR = 0.524, 95%CI 0.402-0.683, p = 1.64 × 10
CONCLUSIONS
Hyperglycemia appeared to promote the mRNA expression of SIRT6 and TETs, which in turn might cause the dynamic changes of 5mC and 5hmC in WBCs from T2DM patients.
Identifiants
pubmed: 30987683
doi: 10.1186/s13148-019-0660-y
pii: 10.1186/s13148-019-0660-y
pmc: PMC6466651
doi:
Substances chimiques
DNA-Binding Proteins
0
Proto-Oncogene Proteins
0
5-hydroxymethylcytosine
1123-95-1
5-Methylcytosine
6R795CQT4H
TET3 protein, human
EC 1.-
Dioxygenases
EC 1.13.11.-
TET2 protein, human
EC 1.13.11.-
SIRT6 protein, human
EC 3.5.1.-
Sirtuins
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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