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 21q22·3. 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 = 1·36 × 10−5, odds ratio (OR) 3·12, 95% confidence interval (CI) 1·87–5·46]. 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 = 4·14 × 10−4, OR 3·00, 95% CI 1·70–5·28). 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 = 0·003, OR 2·49, 95% CI 1·45–4·26).
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.