Sirpa Pahkuri, Ilse Ekman, Céline Vandamme, Kirsti Näntö-Salonen, Jorma Toppari, Riitta Veijola, Mikael Knip, Tuure Kinnunen, Jorma Ilonen & Johanna Lempainen (2023) DNA methylation differences within INS, PTPN22 and IL2RA promoters in lymphocyte subsets in children with type 1 diabetes and controls, Autoimmunity, 56:1, DOI: 10.1080/08916934.2023.2259118
DNA methylation differences within INS, PTPN22 and IL2RA promoters in lymphocyte subsets in children with type 1 diabetes and controls
|Author:||Pahkuri, Sirpa1; Ekman, Ilse2; Vandamme, Céline2;|
1Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
2Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
3Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
4Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, and Centre for Population Health Research, University of Turku, Turku, Finland
5Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland
6Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
7Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
8Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
9Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Eastern Finland Laboratory Centre (ISLAB), Kuopio, Finland
10Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland;j Clinical Microbiology, Turku University Hospital, Turku, Finland
|Online Access:||PDF Full Text (PDF, 2.8 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe20231011139579
|Publish Date:|| 2023-10-11
We elucidated the effect of four known T1D-susceptibility associated single nucleotide polymorphism (SNP) markers in three genes (rs12722495 and rs2104286 in IL2RA, rs689 in INS and rs2476601 in PTPN22) on CpG site methylation of their proximal promoters in different lymphocyte subsets using pyrosequencing. The study cohort comprised 25 children with newly diagnosed T1D and 25 matched healthy controls. The rs689 SNP was associated with methylation at four CpG sites in INS promoter: −234, −206, −102 and −69. At all four CpG sites, the susceptibility genotype AA was associated with a higher methylation level compared to the other genotypes. We also found an association between rs12722495 and methylation at CpG sites −373 and −356 in IL2RA promoter in B cells, where the risk genotype AA was associated with lower methylation level compared to the AG genotype. The other SNPs analyzed did not demonstrate significant associations with CpG site methylation in the examined genes. Additionally, we compared the methylation between children with T1D and controls, and found statistically significant methylation differences at CpG −135 in INS in CD8+ T cells (p = 0.034), where T1D patients had a slightly higher methylation compared to controls (87.3 ± 7.2 vs. 78.8 ± 8.9). At the other CpG sites analyzed, the methylation was similar. Our results not only confirm the association between INS methylation and rs689 discovered in earlier studies but also report this association in sorted immune cells. We also report an association between rs12722495 and IL2RA promoter methylation in B cells. These results suggest that at least part of the genetic effect of rs689 and rs12722495 on T1D pathogenesis may be conveyed by DNA methylation.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3121 General medicine, internal medicine and other clinical medicine
This work was funded by the Sigrid Jusélius Foundation, the Finnish Medical Foundation, and the Päivikki and Sakari Sohlberg –Foundation.
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted manuscript in a repository by the author(s) or with their consent.