P13 AIRE GENE HAPLOTYPE ANALYSIS IN ALOPECIA AREATA
Wengraf D, McDonagh AJG, Birch MP, Messenger AG, Cork MJ, Tazi-Ahnini R
Department of Dermatology & Division of Genomic Medicine, Royal Hallamshire Hospital, University of Sheffield, UNITED KINGDOM

Alopecia areata (AA) is believed to be a T-cell mediated autoimmune disease of the hair follicle. A positive family history occurs in 20-30% of cases, underlining the role of genetic factors in the aetiology. The highest frequency of AA (up to 40 times that in the general population) occurs in the rare recessive Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy syndrome (APECED). APECED is caused by loss-of-function mutations in the Autoimmune Regulator (AIRE) gene, located in the Down syndrome region of human chromosome 21q22.3. The AIRE gene is believed to encode a transcriptional regulator that influences expression of at least 30 genes in the thymus. In a previously published study, we analysed AIRE for its genetic association with AA showing association with the G4144C polymorphism, especially in severe disease (alopecia universalis). In the present work, we have extended our analysis to seven single nucleotide polymorphisms (SNP's) in the AIRE gene at positions T-103C, C2515T, G4144C, T2538C, G6528A, T7215C & T11787C. These were genotyped in 214 cases and 169 matched controls. Only AIRE 4144G and 7215C showed significant association with AA (p=0.005 and p=8x10-7 respectively). Analysis using SNP's to tag the common haplotypes revealed significant association of the haplotype AIRE C-103, G6528, 7215C (CGC) with AA (p<0.0001). Interestingly, the corresponding CGT haplotype seems to have a protective effect, suggesting that the AIRE T7215C variant is responsible for most of the association detected. Furthermore, this association seems to be independent of disease severity. Clinical observations combined with genetic findings suggest that AIRE is a strong candidate gene for AA.