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Tina Rönn

Tina Rönn

Assistant researcher

Tina Rönn

Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets.

Author

  • Tasnim Dayeh
  • Anders H Olsson
  • Petr Volkov
  • Peter Almgren
  • Tina Rönn
  • Charlotte Ling

Summary, in English

AIMS/HYPOTHESIS: To date, the molecular function of most of the reported type 2 diabetes-associated loci remains unknown. The introduction or removal of cytosine-phosphate-guanine (CpG) dinucleotides, which are possible sites of DNA methylation, has been suggested as a potential mechanism through which single-nucleotide polymorphisms (SNPs) can affect gene function via epigenetics. The aim of this study was to examine if any of 40 SNPs previously associated with type 2 diabetes introduce or remove a CpG site and if these CpG-SNPs are associated with differential DNA methylation in pancreatic islets of 84 human donors. METHODS: DNA methylation was analysed using pyrosequencing. RESULTS: We found that 19 of 40 (48%) type 2 diabetes-associated SNPs introduce or remove a CpG site. Successful DNA methylation data were generated for 16 of these 19 CpG-SNP loci, representing the candidate genes TCF7L2, KCNQ1, PPARG, HHEX, CDKN2A, SLC30A8, DUSP9, CDKAL1, ADCY5, SRR, WFS1, IRS1, DUSP8, HMGA2, TSPAN8 and CHCHD9. All analysed CpG-SNPs were associated with differential DNA methylation of the CpG-SNP site in human islets. Moreover, six CpG-SNPs, representing TCF7L2, KCNQ1, CDKN2A, ADCY5, WFS1 and HMGA2, were also associated with DNA methylation of surrounding CpG sites. Some of the type 2 diabetes CpG-SNP sites that exhibit differential DNA methylation were further associated with gene expression, alternative splicing events determined by splice index, and hormone secretion in the human islets. The 19 type 2 diabetes-associated CpG-SNPs are in strong linkage disequilibrium (r (2) > 0.8) with a total of 295 SNPs, including 91 CpG-SNPs. CONCLUSIONS/INTERPRETATION: Our results suggest that the introduction or removal of a CpG site may be a molecular mechanism through which some of the type 2 diabetes SNPs affect gene function via differential DNA methylation and consequently contributes to the phenotype of the disease.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Epigenetics
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2013

Language

English

Pages

1036-1046

Publication/Series

Diabetologia

Volume

56

Issue

5

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Epigenetics

ISBN/ISSN/Other

  • ISSN: 1432-0428