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Exp Clin Endocrinol Diabetes 2019; 127(04): 226-233
DOI: 10.1055/s-0043-121265
Article
© Georg Thieme Verlag KG Stuttgart · New York

Search for Pharmacoepigenetic Correlations in Type 2 Diabetes Under Sulfonylurea Treatment

Makrina Karaglani
1   Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
,
Georgia Ragia
1   Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
,
Maria Panagopoulou
1   Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
,
Ioanna Balgkouranidou
1   Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
,
Evangelia Nena
2   Laboratory of Hygiene and Environmental Protection, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
,
George Kolios
1   Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
,
Nikolaos Papanas
3   Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
,
Vangelis G. Manolopoulos
1   Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
,
Ekaterini Chatzaki
1   Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
› Author Affiliations
Further Information

Publication History

received 17 August 2017
revised 04 October 2017

accepted 06 October 2017

Publication Date:
02 February 2018 (online)

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Abstract

Sulfonylureas are insulin secretagogues which act in pancreatic β cells by blocking the KATP channels encoded by KCNJ11 and ABCC8 genes. In the present study, a pharmacoepigenetic approach was applied for the first time, investigating the correlation of KCNJ11 and ABCC8 gene promoter methylation with sulfonylureas-induced mild hypoglycemic events as well as the KCNJ11 E23K genotype. Sodium bisulfite-treated genomic DNA of 171 sulfonylureas treated T2DM patients previously genotyped for KCNJ11 E23K, including 88 that had experienced drug-associated hypoglycemia and 83 that had never experienced hypoglycemia, were analyzed for DNA methylation of KCNJ11 and ABCC8 gene promoters via quantitative Methylation-Specific PCR. KCNJ11 methylation was detected in 19/88 (21.6%) of hypoglycemic and in 23/83 (27.7%) of non-hypoglycemic patients (p=0.353), while ABCC8 methylation in 6/83 (7.2%) of non-hypoglycemic and none (0/88) of the hypoglycemic patients (p=0.012). Methylation in at least one promoter (KCNJ11 or ABCC8) was significantly associated with non-hypoglycemic patients who are carriers of KCNJ11 EK allele (p=0.030). Our data suggest that ABCC8 but not KCNJ11 methylation is associated to hypoglycemic events in sulfonylureas-treated T2DM patients. Furthermore, it is demonstrated that the KCNJ11 E23K polymorphism in association to either of the two genes’ DNA methylation may have protective role against sulfonylurea-induced hypoglycemia.

Key words

epigenetics - methylation - promoter - receptor - adverse effect

Supplementary Material

 

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