Genome-wide copy number variation (CNV) in patients with autoimmune Addison's disease

BMC Medical Genetics

Research Article

Per M Knappskog¹  Ingeborg Brønstad²  Anette SB Wolff²  Eystein S Husebye³  Kristian Løvås³ 

[1] Institute of Clinical Medicine, University of Bergen, 5021, Bergen, Norway;Department of Medical Genetics, Haukeland University hospital, 5021, Bergen, Norway;Institute of Medicine, University of Bergen, 5021, Bergen, Norway;Institute of Medicine, University of Bergen, 5021, Bergen, Norway;Department of Medicine, Haukeland University hospital, 5021, Bergen, Norway;

关键词: Copy Number Variation;    Copy Number Variation Analysis;    Copy Number Variation Gene;    Copy Number Assay;    Autoimmune Polyendocrine Syndrome;   

DOI  :  10.1186/1471-2350-12-111

 received in 2011-03-30, accepted in 2011-08-18,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundAddison's disease (AD) is caused by an autoimmune destruction of the adrenal cortex. The pathogenesis is multi-factorial, involving genetic components and hitherto unknown environmental factors. The aim of the present study was to investigate if gene dosage in the form of copy number variation (CNV) could add to the repertoire of genetic susceptibility to autoimmune AD.MethodsA genome-wide study using the Affymetrix GeneChip® Genome-Wide Human SNP Array 6.0 was conducted in 26 patients with AD. CNVs in selected genes were further investigated in a larger material of patients with autoimmune AD (n = 352) and healthy controls (n = 353) by duplex Taqman real-time polymerase chain reaction assays.ResultsWe found that low copy number of UGT2B28 was significantly more frequent in AD patients compared to controls; conversely high copy number of ADAM3A was associated with AD.ConclusionsWe have identified two novel CNV associations to ADAM3A and UGT2B28 in AD. The mechanism by which this susceptibility is conferred is at present unclear, but may involve steroid inactivation (UGT2B28) and T cell maturation (ADAM3A). Characterization of these proteins may unravel novel information on the pathogenesis of autoimmunity.

【 授权许可】

Unknown   
© Brønstad et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.