Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets.
Dayeh, Tasnim LU ; Olsson, Anders H LU ; Volkov, Petr LU ; Almgren, Peter LU ; Rönn, Tina LU and Ling, Charlotte LU
(2013)
In Diabetologia
56(5).
p.1036-1046
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3628602
- author
- Dayeh, Tasnim
LU
; Olsson, Anders H
LU
; Volkov, Petr
LU
; Almgren, Peter
LU
; Rönn, Tina
LU
and Ling, Charlotte
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetologia
- volume
- 56
- issue
- 5
- pages
- 1036 - 1046
- publisher
- Springer
- external identifiers
-
- wos:000318787100011
- pmid:23462794
- scopus:84876458561
- ISSN
- 1432-0428
- DOI
- 10.1007/s00125-012-2815-7
- language
- English
- LU publication?
- yes
- id
- b09872b3-2abb-44d8-a7ad-f80c933f885f (old id 3628602)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23462794?dopt=Abstract
- date added to LUP
- 2016-04-01 10:23:06
- date last changed
- 2024-05-05 12:02:51
@article{b09872b3-2abb-44d8-a7ad-f80c933f885f,
abstract = {{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.}},
author = {{Dayeh, Tasnim and Olsson, Anders H and Volkov, Petr and Almgren, Peter and Rönn, Tina and Ling, Charlotte}},
issn = {{1432-0428}},
language = {{eng}},
number = {{5}},
pages = {{1036--1046}},
publisher = {{Springer}},
series = {{Diabetologia}},
title = {{Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets.}},
url = {{https://lup.lub.lu.se/search/files/1801686/3810053.pdf}},
doi = {{10.1007/s00125-012-2815-7}},
volume = {{56}},
year = {{2013}},
}