TY  - JOUR
A1  - Wolff, Anette Susanne Bøe
A1  - Mitchell, Anna L.
A1  - Cordell, Heather J.
A1  - Short, Andrea
A1  - Skinningsrud, Beate
A1  - Ollier, William
A1  - Badenhoop, Klaus
A1  - Meyer, Gesine
A1  - Falorni, Alberto
A1  - Kämpe, Olle
A1  - Undlien, Dag
A1  - Pearce, Simon H. S.
A1  - Husebye, Eystein S.
T1  - CTLA-4 as a genetic determinant in autoimmune Addison's disease
T2  - Genes and immunity
N2  - 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.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/40424
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-404241
SN  - 1466-4879
SN  - 1476-5470
N1  - 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/.
VL  - 16
SP  - 430
EP  - 436
PB  - Nature Publ. Group
CY  - Basingstoke
ER  -