Linked Life Data

12542742

Source:http://linkedlifedata.com/resource/pubmed/id/12542742

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-1-24
pubmed:abstractText
Alopecia areata is characterized by a reversible form of patchy or complete hair loss associated with T-cell infiltration of hair follicles. The lifetime disease risk of approximately 1.4% in the general population is increased to more than 30% in autoimmune polyendocrinopathy candidiasis ectodermal dysplasia syndrome (APECED), a recessive condition resulting from a mutation of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. Aire protein is thought to have transcriptional regulatory activity but its role is not well defined at present. In this study, we have examined the possible involvement of AIRE in the pathogenesis of alopecia areata. On screening the AIRE coding sequence, we identified 20 variants. Two of these at positions, G961C and T1029C, give rise to amino acid changes, S278R and V301A, located in the DNA-binding segment (SAND) and PHD1 zinc finger motif, respectively. We found no difference in the frequency of the AIRE T1029C polymorphism between the control and patient groups. We genotyped 202 alopecia areata patients and 175 matched Caucasian controls for the AIRE G961C alleles. The frequency of the rare allele (961G) was 0.08 in the controls and there was a significant increase to 0.13 in alopecia areata overall and 0.20 in severe disease (alopecia universalis). We found no association between the AIRE G961G variant and mild (patchy) alopecia areata or alopecia totalis. However, the AIRE 961G allele is a potent risk factor (> 3) for the severest form of alopecia areata, and for disease of early age at onset (at 30 years). The change from serine to arginine in the SAND domain of AIRE protein may have a significant effect on AIRE DNA-binding activity. Moreover, our results could provide a rational explanation of the unusually high frequency of AA in APECED patients, supporting the concept of AA as an autoimmune disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0001-2815
pubmed:author
pubmed:issnType
Print
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
489-95
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Role of the autoimmune regulator (AIRE) gene in alopecia areata: strong association of a potentially functional AIRE polymorphism with alopecia universalis.
pubmed:affiliation
Division of Genomic Medicine, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK. r.taziahnini@sheffield.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't