title: Genetic analysis of autoimmune regulator haplotypes in alopecia areata.
abstract: Alopecia areata is an immune-mediated disorder, occurring with the highest observed frequency in the rare recessive autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome caused by mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. We have previously detected association between alopecia areata and a single nucleotide polymorphism (SNP) in the AIRE gene in patients without APECED, and we now report the findings of an extended examination of the association of alopecia areata with haplotype analysis including six SNPs in the AIRE gene: C-103T, C4144G, T5238C, G6528A, T7215C and T11787C. In Caucasian groups of 295 patients and 363 controls, we found strong association between the AIRE 7215C allele and AA [P = 3.8 x 10(-8), OR (95% CI): 2.69 (1.8-4.0)]. The previously reported association between AA and the AIRE 4144G allele was no longer significant on correction for multiple testing. The AIRE haplotypes CCTGCT and CGTGCC showed a highly significant association with AA [P = 6.05 x 10(-6), 9.47 (2.91-30.8) and P = 0.001, 3.51 (1.55-7.95), respectively]. To select the haplotypes most informative for analysis, we tagged the polymorphisms using SNPTag software. Employing AIRE C-103T, G6528A, T7215C and T11787C as tag SNPs, two haplotypes were associated with AA; AIRE CGCT and AIRE CGCC [P = 3.84 x 10(-7), 11.40 (3.53-36.9) and P = 3.94 x 10(-4), 2.13 (1.39-3.24) respectively]. The AIRE risk haplotypes identified in this study potentially account for a major component of the genetic risk of developing alopecia areata.
authors.affiliation: School of Medicine & Biomedical Sciences, University of Sheffield, Sheffield, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Wengraf
authors.forename: A J G
authors.initials: AJ
authors.lastname: McDonagh
authors.forename: T R J
authors.initials: TR
authors.lastname: Lovewell
authors.forename: Y
authors.initials: Y
authors.lastname: Vasilopoulos
authors.forename: S P
authors.initials: SP
authors.lastname: Macdonald-Hull
authors.forename: M J
authors.initials: MJ
authors.lastname: Cork
authors.forename: A G
authors.initials: AG
authors.lastname: Messenger
authors.forename: R
authors.initials: R
authors.lastname: Tazi-Ahnini
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000506:Alopecia Areata / Q000235:genetics* / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D012313:RNA; D014157:Transcription Factors; D000096927:AIRE Protein