R. Tazi-Ahnini, A.J.G. McDonagh, D.A. Wengraf, T.R.J. Lovewell, Y. Vasilopoulos, A.G. Messenger, M.J. Cork and D.J. Gawkrodger_

*Division of Genomic Medicine, University of Sheffield, Sheffield S10 2RX, U.K._Dermatology Immunogenetics Group, University of Sheffield, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K.Correspondence
R. Tazi-Ahnini.

Accepted for publication
19 November 2007
Key words
AIRE gene, autoimmunity, genetics, vitiligo
Summary
Background: Vitiligo is an autoimmune disorder that occurs with greatly increased frequency in the rare recessive autoimmune polyendocrinopathy–candidiasis– ectodermal dystrophy syndrome (APECED) caused by mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22Ж3. We have previously detected an association between alopecia areata and single nucleotide polymorphisms (SNPs) in the AIRE gene.
Objectives: To report the findings of an extended study including haplotype analysis on six AIRE polymorphisms (AIRE C–103T, C4144G, T5238C, G6528A, T7215C and T11787C) in vitiligo, another APECED-associated disease.
Methods: A case–control analysis was performed.
Results: Results showed a strong association between AIRE 7215C and vitiligo [P = 1Ж36 ・ 10)5, odds ratio (OR) 3Ж12, 95% confidence interval (CI) 1Ж87– 5Ж46]. We found no significant association with the other polymorphisms individually.
However, haplotype analysis revealed that the AIRE haplotype CCTGCC
showed a highly significant association with vitiligo (P = 4Ж14 ・ 10)4, OR 3Ж00, 95% CI 1Ж70–5Ж28). To select the most informative minimal haplotypes, we
tagged the polymorphisms using SNP tag software. Using AIRE C–103T, G6528A,
T7215C and T11787C as tag SNPs, the haplotype AIRE CGCC was associated with
vitiligo (P = 0Ж003, OR 2Ж49, 95% CI 1Ж45–4Ж26).
Conclusions: The link between vitiligo and AIRE raises the possibility that defective skin peripheral antigen selection in the thymus is involved in the changes that result in melanocyte destruction in this disorder.