Altered DNA methylation profile in Norwegian patients with Autoimmune Addison's Disease

Trine E Bjanesoy; Bettina Kulle Andreassen; Eirik Bratland; Andrew Reiner; Shahinul Islam; Eystein S Husebye; Marit Bakke

doi:10.1016/j.molimm.2014.02.018

Altered DNA methylation profile in Norwegian patients with Autoimmune Addison's Disease

Mol Immunol. 2014 Jun;59(2):208-16. doi: 10.1016/j.molimm.2014.02.018. Epub 2014 Mar 22.

Authors

Trine E Bjanesoy¹, Bettina Kulle Andreassen², Eirik Bratland³, Andrew Reiner⁴, Shahinul Islam¹, Eystein S Husebye⁵, Marit Bakke⁶

Affiliations

¹ Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.
² Department of Molecular Biology, Institute of Clinical Medicine, University of Oslo, P.O Box 1171, 0318 Oslo, Norway; Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, P.O Box 1110, 0317 Oslo, Norway.
³ Department of Clinical Science, University of Bergen, P.O Box 7804, 5020 Bergen, Norway.
⁴ Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O Box 1110, 0317 Oslo, Norway.
⁵ Department of Clinical Science, University of Bergen, P.O Box 7804, 5020 Bergen, Norway; Department of Medicine, Haukeland University Hospital, P.O Box 7804, 5020 Bergen, Norway.
⁶ Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway. Electronic address: Marit.Bakke@biomed.uib.no.

PMID: 24667071
DOI: 10.1016/j.molimm.2014.02.018

Abstract

Autoimmune Addison's Disease (AAD) is an endocrine and immunological disease of uncertain pathogenesis resulting from the immune system's destruction of the hormone producing cells of the adrenal cortex. The underlying molecular mechanisms are largely unknown, but it is commonly accepted that a combination of genetic susceptibility and environmental impact is critical. In the present study, we identified multiple hypomethylated gene promoter regions in patients with isolated AAD using DNA isolated from CD4+ T cells. The identified differentially methylated regions were distributed evenly across the 10.5-kb-promoter regions covered by the array, and a substantial number localized to promoters of genes involved in immune regulation and autoimmunity. This study reveals a hypomethylated status in CD4+ T cells from AAD patients and indicates differential methylation of promoters of key genes involved in immune responses.

Keywords: Adrenal gland; Autoimmune Addison's Disease; Autoimmunity; DNA methylation; Epigenetics.

MeSH terms

Addison Disease / genetics*
Addison Disease / immunology
Adrenal Cortex / cytology
Adrenal Cortex / immunology
Adult
Autoimmunity / immunology
CD4-Positive T-Lymphocytes / cytology
DNA Methylation*
Female
Genetic Predisposition to Disease
Humans
Middle Aged
Norway
Promoter Regions, Genetic / genetics*
Young Adult