title: AIRE variations in Addison's disease and autoimmune polyendocrine syndromes (APS): partial gene deletions contribute to APS I.
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.
authors.affiliation: Institute of Medicine, University of Bergen, Bergen, Norway. Anette.boe@med.uib.no
authors.forename: A S
authors.initials: AS
authors.lastname: Bøe Wolff
authors.forename: B
authors.initials: B
authors.lastname: Oftedal
authors.forename: S
authors.initials: S
authors.lastname: Johansson
authors.forename: O
authors.initials: O
authors.lastname: Bruland
authors.forename: K
authors.initials: K
authors.lastname: Løvås
authors.forename: A
authors.initials: A
authors.lastname: Meager
authors.forename: C
authors.initials: C
authors.lastname: Pedersen
authors.forename: E S
authors.initials: ES
authors.lastname: Husebye
authors.forename: P M
authors.initials: PM
authors.lastname: Knappskog
mesh_terms: D000224:Addison Disease / Q000453:epidemiology / Q000235:genetics*; D017353:Gene Deletion; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D016884:Polyendocrinopathies, Autoimmune / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein