Anette Susanne Bøe Wolff, Anna L. Mitchell, Heather J. Cordell, Andrea Short, Beate Skinningsrud, William Ollier, Klaus Badenhoop, Gesine Meyer, Alberto Falorni, Olle Kämpe, Dag Undlien, Simon H. S. Pearce, Eystein S. Husebye
- In common with several other autoimmune diseases, autoimmune Addison's disease (AAD) is thought to be caused by a combination of deleterious susceptibility polymorphisms in several genes, together with undefined environmental factors and stochastic events. To date, the strongest genomic association with AAD has been with alleles at the HLA locus, DR3-DQ2 and DR4. The contribution of other genetic variants has been inconsistent. We have studied the association of 16 single-nucleotide polymorphisms (SNPs) within the CD28-CTLA-4-ICOS genomic locus, in a cohort comprising 691 AAD patients of Norwegian and UK origin with matched controls. We have also performed a meta-analysis including 1002 patients from European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10-1.66), P=0.004), but not in UK patients. The same allele is associated with AAD in the total European population (OR=1.37 (CI 1.13-1.66), P=0.002). A three-marker haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68-3.51), P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for the development of AAD, and refines its mapping within the wider genomic locus.
MetadatenAuthor: | Anette Susanne Bøe Wolff, Anna L. Mitchell, Heather J. Cordell, Andrea Short, Beate Skinningsrud, William Ollier, Klaus BadenhoopORCiDGND, Gesine MeyerORCiDGND, Alberto Falorni, Olle Kämpe, Dag Undlien, Simon H. S. Pearce, Eystein S. Husebye |
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URN: | urn:nbn:de:hebis:30:3-404241 |
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DOI: | https://doi.org/10.1038/gene.2015.27 |
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ISSN: | 1466-4879 |
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ISSN: | 1476-5470 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/26204230 |
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Parent Title (English): | Genes and immunity |
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Publisher: | Nature Publ. Group |
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Place of publication: | Basingstoke |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2015/07/23 |
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Date of first Publication: | 2015/07/23 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2016/06/10 |
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Volume: | 16 |
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Page Number: | 7 |
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First Page: | 430 |
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Last Page: | 436 |
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Note: | This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/. |
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HeBIS-PPN: | 428607616 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen |
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