Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Biomedical Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9434 Online ISSN: 2049-9442
Journal Cover
October-2020 Volume 13 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
October-2020 Volume 13 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes

  • Authors:
    • Konstantina Mouzaki
    • Eleni P. Kotanidou
    • Aikaterini Fragou
    • Ioannis Kyrgios
    • Styliani Giza
    • Angeliki Kleisarchaki
    • Vasiliki Rengina Tsinopoulou
    • Anastasios Serbis
    • Georgios Tzimagiorgis
    • Assimina Galli‑Τsinopoulou
  • View Affiliations / Copyright

    Affiliations: Second Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA General Hospital, 546 36 Thessaloniki, Greece, Laboratory of Biological Chemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54 124 Thessaloniki, Greece
  • Article Number: 31
    |
    Published online on: July 31, 2020
       https://doi.org/10.3892/br.2020.1338
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The insulin (INS) gene is the one of the most important genes involved in the pathogenesis of Type 1 Diabetes (T1D) after the Major Histocompatibility Complex genes. Studies addressing the issue of hyper‑ or hypo‑methylation status of the INS gene promoter have reported inconsistent results. The majority of studies showed hypomethylation; however a few studies have shown hypermethylation at specific cytosine‑guanosine (CpG) sites in the promoter region of the INS gene. The aim of the present study was to analyze the methylation status of the promoter region of the INS gene in Greek children and adolescents with T1D. A total of 20 T1D participants (mean diabetes duration of 6.15±4.12 years) and 20 age‑ and sex‑matched controls were enrolled in the present study. DNA was isolated from whole blood samples, modified using sodium bisulfite and analyzed using PCR and electrophoresis. DNA was then pooled with highly reactive supermagnetic beads at similar molar quantities, submitted for library construction and finally sequenced using next‑generation sequencing. The methylation profile at 10 CpG sites around the transcription start site (TSS) of the INS promoter was analysed and expressed as the mean ± standard deviation. The overall mean methylation in patients with T1D did not differ compared with the healthy controls. There was a statistically significant difference between the two groups in hypermethylation at position ‑345 (P=0.02), while a trend (P=0.06) at position ‑102 was observed. According to the results of the present study, increased methylation in the INS gene promoter at specific CpG sites around the TSS were already present in childhood T1D. These data may possibly serve as a guide towards the identification of a methylation pattern for detection of development of T1D in genetically predisposed children.
View Figures

Figure 1

Figure 2

View References

1 

Pugliese A: The insulin gene in type 1 diabetes. IUBMB Life. 57:463–468. 2005.PubMed/NCBI View Article : Google Scholar

2 

Steck AK and Rewers MJ: Genetics of type 1 diabetes. Clin Chem. 57:176–185. 2011.PubMed/NCBI View Article : Google Scholar

3 

Bansal A and Pinney SE: DNA methylation and its role in the pathogenesis of diabetes. Pediatr Diabetes. 18:167–177. 2017.PubMed/NCBI View Article : Google Scholar

4 

Handy DE, Castro R and Loscalzo J: Epigenetic modifications: Basic mechanism and role in cardiovascular disease. Circulation. 17:2145–2156. 2011.PubMed/NCBI View Article : Google Scholar

5 

Cano-Rodriguez D and Rots MG: Epigenetic editing: On the verge of reprogramming gene expression at will. Curr Genet Med Rep. 1:170–179. 2016.PubMed/NCBI View Article : Google Scholar

6 

Dang MN, Buzzetti R and Pozzilli P: Epigenetics in autoimmune diseases with focus on type 1 diabetes. Diabetes Metab Res Rev. 29:8–18. 2013.PubMed/NCBI View Article : Google Scholar

7 

Wang Z, Xie Z, Lu Q, Chang C and Zhou Z: Beyond genetics: What causes type 1 diabetes. Clin Rev Allergy Immunol. 52:273–286. 2017.PubMed/NCBI View Article : Google Scholar

8 

Moore LD, Le T and Fan G: DNA methylation and its basic function. Neuropsychopharmacology. 38:23–38. 2013.PubMed/NCBI View Article : Google Scholar

9 

Deaton AM and Bird A: CpG islands and the regulation of transcription. Genes Dev. 15:1010–1022. 2011.PubMed/NCBI View Article : Google Scholar

10 

Riu J, Deng S, Lebastchi J, Clark PL, Usmani-Brawn S and Herold KC: Methylation of insulin DNA in response to proinflammatory cytokines during the progression of autoimmune diabetes in NOD mice. Diabetologia. 59:1021–1029. 2016.PubMed/NCBI View Article : Google Scholar

11 

Zhang K, Lin G, Han Y, Xie J and Li J: Circulating unmethylated insulin DNA as a potential non-invasive biomarker of beta cell death in type 1 diabetes: A review and future prospect. Clin Epigenetics. 26(44)2017.PubMed/NCBI View Article : Google Scholar

12 

Husseiny MI, Kaye A, Zebabua E, Kandeel F and Ferreri K: Tissue-specific methylation of human insulin gene and PCR assay for monitoring beta cell death. PLoS One. 9(e94591)2014.PubMed/NCBI View Article : Google Scholar

13 

Neiman D, Moss J, Hecht M, Magenheim J, Piyanzin S, Shapiro AM, de Koning EJ, Razin A, Cedar H, Shemer R and Dor Y: Islet cells share promoter hypomethylation independently of expression, but exhibit cell-type-specific methylation in enhancers. Proc Natl Acad Sci USA. 19:13525–13230. 2017.PubMed/NCBI View Article : Google Scholar

14 

Fradin D, Le Fur S, Mille C, Naoui N, Groves C, Zelenika D, McCarthy MI, Lathrop M and Bougnères P: Association of the CpG methylation pattern of the proximal insulin gene promoter with type 1 diabetes. PLoS One. 7(336278)2012.PubMed/NCBI View Article : Google Scholar

15 

Fisher MM, Watkins RA, Blum J, Evans-Molina C, Chalasani N, DiMeglio LA, Mather KJ, Tersey SA and Mirmira RG: Elevations in circulating methylated and unmethylated preproinsulin DNA in new-onset type 1 diabetes. Diabetes. 64:3867–3872. 2015.PubMed/NCBI View Article : Google Scholar

16 

Lehmann-Werman R, Neiman D, Zemmour H, Moss J, Magenheim J, Vaknin-Dembinsky A, Rubertsson S, Nellgård B, Blennow K, Zetterberg H, et al: Identification of tissue-specific cell death using methylation patterns of circulating DNA. Proc Natl Acad Sci USA. 113:E1826–E1834. 2016.PubMed/NCBI View Article : Google Scholar

17 

Kuroda A, Rauch TA, Todorov I, Ku HT, Al-Abdullah I, Kandeel F, Mullen Y, Pfeifer GP and Ferreri K: Insulin gene expression is regulated by DNA methylation. PLoS One. 9(e6953)2009.PubMed/NCBI View Article : Google Scholar

18 

Herold KC, Usmani-Brown S, Ghazi T, Lebastchi J, Beam CA, Bellin MD, Ledizet M, Sosenko JM, Krischer JP and Palmer JP: Type 1 Diabetes TrialNet Study Group. β cell death and dysfunction during type 1 diabetes development in at-risk individuals. J Clin Invest. 125:1163–1173. 2015.PubMed/NCBI View Article : Google Scholar

19 

Mayer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX, Aschner P and Craig ME: ISPAD Clinical practice consensus guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 19:7–19. 2018.PubMed/NCBI View Article : Google Scholar

20 

American Diabetes Association. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2018. Diabetes Care. 41 (Suppl 1):S13–S27. 2018.PubMed/NCBI View Article : Google Scholar

21 

Marshall WA and Tanner JM: Variations in the pattern of pubertal changes in boys. Arch Dis Child. 45:13–23. 1970.PubMed/NCBI View Article : Google Scholar

22 

Marshall WA and Tanner JM: Variations in pattern of pubertal changes in girls. Arch Dis Child. 44:291–303. 1969.PubMed/NCBI View Article : Google Scholar

23 

World Medical Association. World medical association declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA. 310:2191–2194. 2013.PubMed/NCBI View Article : Google Scholar

24 

Li Y and Tollefsbol TO: DNA methylation detection: Bisulfite genomic sequencing analysis. Methods Mol Biol. 791:11–21. 2011.PubMed/NCBI View Article : Google Scholar

25 

Scala G, Affinito O, Palumbo D, Florio E, Monticelli A, Miele G, Chiariotti L and Cocozza S: AmpliMethProfiler: A pipeline for the analysis of CpG methylation profiles of targeted deep bisulfite sequenced amplicons. BMC Bioinformatics. 25(484)2016.PubMed/NCBI View Article : Google Scholar

26 

Mirmira RG, SimsEK Syed F and Evans-Morina C: Biomarkers of β-cell stress and death in type 1 diabetes. Curr Diab Rep. 16(95)2016.PubMed/NCBI View Article : Google Scholar

27 

Husseiny MI, Kuroda A, Kaye AN, Nair I, Kandeel F and Ferreri K: Development of a quantitative methylation-specific polymerase chain reaction method for monitoring beta cell death in type 1 diabetes. PLoS One. 7(e47942)2012.PubMed/NCBI View Article : Google Scholar

28 

Fisher MM, Chumbiauca CN, Mather KJ, Mirmira RG and Tersey SA: Detection of islet β-cell death in vivo by multiplex PCR analysis of differentially methylated DNA. Endocrinology. 154:3476–3481. 2013.PubMed/NCBI View Article : Google Scholar

29 

Usmani-Brown S, Lebastchi J, Steck AK, Beam S, Herold KC and Ledizet M: Analysis of β-cell death in type 1 diabetes by droplet digital PCR. Endocrinol. 155:3694–3698. 2014.PubMed/NCBI View Article : Google Scholar

30 

Akirav EM, Lebastchi J, Galvan EM, Henegariu O, Akirav M, Ablamunits V, Lizardi PM and Herold KC: Detection of β cell death in diabetes using differentially methylated circulating DNA. Proc Natl Acad Sci USA. 108:19018–19023. 2011.PubMed/NCBI View Article : Google Scholar

31 

Grada A and Weinbrecht K: Next generation sequencing: Methodology and application. J Invest Dermatol. 133(e11)2013.PubMed/NCBI View Article : Google Scholar

32 

Behjati S and Tarpey PS: What is next generation sequencing? Arch Dis Child Educ Pract Ed. 98:236–238. 2013.PubMed/NCBI View Article : Google Scholar

33 

Liu L, Li Y, Li S, Hu N, He Y, Pong R, Lin D, Lu L and Law M: Comparison of next generation sequencing systems. J Biomed Biotechnol. 2012(251364)2012.PubMed/NCBI View Article : Google Scholar

34 

Buermans HPJ and den Dunnen JT: Next generation sequencing technology: Advantages and applications. Biochim Biophys Acta. 1842:1932–1941. 2014.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Mouzaki K, Kotanidou EP, Fragou A, Kyrgios I, Giza S, Kleisarchaki A, Tsinopoulou VR, Serbis A, Tzimagiorgis G, Galli‑Τsinopoulou A, Galli‑Τsinopoulou A, et al: Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes. Biomed Rep 13: 31, 2020.
APA
Mouzaki, K., Kotanidou, E.P., Fragou, A., Kyrgios, I., Giza, S., Kleisarchaki, A. ... Galli‑Τsinopoulou, A. (2020). Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes. Biomedical Reports, 13, 31. https://doi.org/10.3892/br.2020.1338
MLA
Mouzaki, K., Kotanidou, E. P., Fragou, A., Kyrgios, I., Giza, S., Kleisarchaki, A., Tsinopoulou, V. R., Serbis, A., Tzimagiorgis, G., Galli‑Τsinopoulou, A."Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes". Biomedical Reports 13.4 (2020): 31.
Chicago
Mouzaki, K., Kotanidou, E. P., Fragou, A., Kyrgios, I., Giza, S., Kleisarchaki, A., Tsinopoulou, V. R., Serbis, A., Tzimagiorgis, G., Galli‑Τsinopoulou, A."Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes". Biomedical Reports 13, no. 4 (2020): 31. https://doi.org/10.3892/br.2020.1338
Copy and paste a formatted citation
x
Spandidos Publications style
Mouzaki K, Kotanidou EP, Fragou A, Kyrgios I, Giza S, Kleisarchaki A, Tsinopoulou VR, Serbis A, Tzimagiorgis G, Galli‑Τsinopoulou A, Galli‑Τsinopoulou A, et al: Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes. Biomed Rep 13: 31, 2020.
APA
Mouzaki, K., Kotanidou, E.P., Fragou, A., Kyrgios, I., Giza, S., Kleisarchaki, A. ... Galli‑Τsinopoulou, A. (2020). Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes. Biomedical Reports, 13, 31. https://doi.org/10.3892/br.2020.1338
MLA
Mouzaki, K., Kotanidou, E. P., Fragou, A., Kyrgios, I., Giza, S., Kleisarchaki, A., Tsinopoulou, V. R., Serbis, A., Tzimagiorgis, G., Galli‑Τsinopoulou, A."Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes". Biomedical Reports 13.4 (2020): 31.
Chicago
Mouzaki, K., Kotanidou, E. P., Fragou, A., Kyrgios, I., Giza, S., Kleisarchaki, A., Tsinopoulou, V. R., Serbis, A., Tzimagiorgis, G., Galli‑Τsinopoulou, A."Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes". Biomedical Reports 13, no. 4 (2020): 31. https://doi.org/10.3892/br.2020.1338
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team