1. ¹Institute of Medicine, University of Bergen, Bergen, Norway
2. ²Department of Medicine, Haukeland University Hospital, Bergen, Norway
3. ³Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
4. ⁴Department of Clinical Medicine, University of Bergen, Bergen, Norway
5. ⁵Biotherapeutics Group, The National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Herts, UK
6. ⁶Department of Pediatrics, Kolding Hospital, Kolding, Denmark

Correspondence: Dr AS Bøe Wolff, Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen N-5021, Norway. E-mail: Anette.boe@med.uib.no

⁷These authors contributed equally to this work.

Received 2 November 2007; Revised 19 November 2007; Accepted 26 November 2007; Published online 17 January 2008.

Abstract

Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms or copy number variations in the AIRE gene were associated with AAD and APS II. First, nine SNPs in the AIRE gene were analyzed in 311 patients with AAD and APS II and 521 healthy controls, identifying no associated risk. Second, in a subgroup of 25 of these patients, AIRE sequencing revealed three novel polymorphisms. Finally, the AIRE copy number was determined by duplex quantitative PCR in 14 patients with APS I, 161 patients with AAD and APS II and in 39 healthy subjects. In two Scandinavian APS I patients previously reported to be homozygous for common AIRE mutations, we identified large deletions of the AIRE gene covering at least exon 2 to exon 8. We conclude that polymorphisms in the AIRE gene are not associated with AAD and APS II. We further suggest that DNA analysis of the parents of patients found to be homozygous for mutations in AIRE, always should be performed.