The autoimmune regulator gene (AIRE) is strongly associated with vitiligo

Division of Genomic Medicine, University of Sheffield, Sheffield S10 2RX, UK.
British Journal of Dermatology (Impact Factor: 4.28). 08/2008; 159(3):591-6. DOI: 10.1111/j.1365-2133.2008.08718.x
Source: PubMed


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.
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.
A case-control analysis was performed.
Results showed a strong association between AIRE 7215C and vitiligo [P = 1.36 x 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 x 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).
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.

Download full-text


Available from: Yiannis Vasilopoulos, May 21, 2015
  • Source
    • "Several candidate genes have been linked to vitiligo [13], such as genes involved in the leukocyte antigen system (HLA, MIM 615161), cytotoxic T lymphocyte-associated 4 (CTLA4, MIM 123890), tumor necrosis factors (TNFí µí»¼, MIM 191160), and autoimmune regulators (AIRE gene, MIM 607358) [14]. Transporter associated with antigen processing (TAP) genes are encoded in the MHC-II region of the human HLA locus (MIM 615161). "
    [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated whether TAP1-rs1135216 (p.637D>G) and PSMB9-rs17587 (p.60R>H) were significantly associated with the risk and severity of vitiligo among Saudi patients. One hundred seventy-two subjects were genotyped for the TAP1-rs1135216 and PSMB9-rs17587 variants using endonuclease digestions of amplified genomic DNA. The TAP1-rs1135216 and PSMB9-rs17587 mutant alleles were strongly associated with vitiligo, with odds ratios showing five fold and two fold risks ( P < 0.0001 and P = 0.007 , resp.). In TAP1-rs1135216, the 637G mutant allele was more frequent in cases (74%) than in healthy controls. In cases, the 60H mutant allele PSMB9-rs17587 was less frequent (42%) than the wild-type 60R allele (58%). Vitiligo vulgaris was the most common type of disease, associated with the DG (55%) and GG (46%) genotypes for rs1135216 and with the RH genotype (59%) for rs17587. The heterozygous 637DG and 60RH genotypes were each linked with active phenotypes in 64% of cases. In conclusion, the TAP1-rs1135216 and PSMB9-rs17587 variants are significantly associated with vitiligo, and even one copy of these mutant alleles can influence the risk among Saudis. Vitiligo vulgaris is associated with genotypes containing the mutant G and H alleles.
    Full-text · Article · Dec 2014 · Disease markers
  • Source
    • "Skin changes have been reported as part of several systemic rheumatic disorders in both humans and dogs, especially in those cases with a probable SLE diagnosis [2,6,9,11,27]. One of the Tollers with a homogeneous IIF-ANA pattern showed vitiligo and another dog showed plasmacytic and pyogranulomatous dermatitis, both of these disorders with a probable immune-mediated origin [30,31]. However, the other four dogs with skin problems displayed unspecific lesions whose background is unclear. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A disease complex with chronic musculoskeletal signs, including stiffness and joint pain, and to which there is a strong predisposition in the canine breed Nova Scotia duck tolling retriever (Toller) has been recognized in Sweden. The aim of this first clinical description of the disorder in Tollers was to describe the clinical manifestations and laboratory findings, as well as to try to identify a possible immune-mediated background of the disease and to show the outcome of treatment in 33 Tollers. The study included 33 Tollers with musculoskeletal signs and 20 healthy controls. All the dogs were thoroughly examined and followed for a period of 2 months - 4 years. An IIF-ANA (antinuclear antibody) test and an assay for the presence of antibodies to Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato were performed, as well as some haematology, serum biochemistry and urine tests. Routine radiographic examinations were performed on 11 dogs. All the Toller patients showed stiffness and lameness that had lasted for at least 14 days and displayed pain from several joints of extremities on manipulation. Twenty-seven per cent of the dogs also showed muscle pain and 18% different skin symptoms. Seventy per cent of the Tollers with signs of disease displayed a positive IIF-ANA test. Most of the dogs were treated with corticosteroids, with the majority of the dogs (65%) showing good responses. There was no association between the IIF-ANA results and the clinical signs or results of treatment. This paper describes a disorder in Nova Scotia duck tolling retrievers where the clinical signs, ANA reactivity and response to corticosteroids strongly suggest that the disorder is immune-mediated. The findings of this research may indicate a chronic systemic rheumatic disorder.
    Full-text · Article · Apr 2009 · Acta Veterinaria Scandinavica
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-12 (IL-12) p70 is an important cytokine secreted by antigen-presenting cells in response to antigenic stimulation; it is a heterodimer of p35 and p40 subunits. Here, we report a new, highly sensitive, and reliable method that employs fluorometric sandwich ELISA for quantification of the mouse IL-12 (moIL-12) p70 protein. Our method could quantify moIL-12 p70 in the range of approximately 0.5 to 500 pg/ml. In the assay, no signals were produced by the moIL-12 p40 monomer, homodimer [(p40)2], or mouse IL-23 even up to a concentration of 500 pg/ml; this ensures that our assay has a high specificity for moIL-12 p70. To demonstrate that our method can determine natural moIL-12 in real physiological/pathological samples, we monitored the moIL-12 p70 secretion from peritoneal exudative cells after lipopolysaccharide (LPS) stimulation. IL-12 p70 secretion as early as 3h after LPS stimulation was reliably detected due to the high sensitivity of the method.
    Full-text · Article · Mar 2007 · Cell Biology International
Show more