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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2011

Open Access 01-12-2011 | Research article

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

Authors: Ingeborg Brønstad, Anette SB Wolff, Kristian Løvås, Per M Knappskog, Eystein S Husebye

Published in: BMC Medical Genetics | Issue 1/2011

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Abstract

Background

Addison'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.

Methods

A 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.

Results

We 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.

Conclusions

We 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.
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Metadata
Title
Genome-wide copy number variation (CNV) in patients with autoimmune Addison's disease
Authors
Ingeborg Brønstad
Anette SB Wolff
Kristian Løvås
Per M Knappskog
Eystein S Husebye
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2011
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-12-111

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