Source:http://linkedlifedata.com/resource/pubmed/id/11841485
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2002-2-13
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pubmed:abstractText |
Alopecia areata is an inflammatory hair loss disease with a major genetic component. The presence of focal inflammatory lesions with perifollicular T-cell infiltrates reflects the importance of local cytokine production in the pathogenesis. In addition to its fundamental pro-inflammatory role, the interleukin-1 (IL-1) system has major effects on hair growth regulation in vitro, with the inhibitory actions of IL-1alpha and IL-1beta being opposed by the receptor antagonist IL-1ra. The novel interleukin-1 like molecule 1 (IL-1L1) which has greatest gene sequence homology with IL1RN, the gene encoding IL-1ra, is another potential IL-1 antagonist. In view of previous studies suggesting a significant role for IL1RN polymorphisms in the pathogenesis of autoimmune/inflammatory disease, we have analysed polymorphisms of IL-1ra (IL1RN+2018) and its homologue IL-1L1 (IL1L1+4734) in a case-control association study on 165 patients and a large number of matched controls. Homozygosity for the rare allele of IL1RN (IL1RN*2) was significantly associated with alopecia areata [odds ratio (OR) = 1.89, 95% CI (1.09, 3.28); P = 0.02], confirming our previous findings of significant association with the IL1RN variable number tandem repeat (VNTR). The results also revealed a novel association involving a polymorphism of the interleukin-1 receptor antagonist homologue IL1L1 at position + 4734, IL1RN+2018, and alopecia areata. The effect of a genotype combining three copies of the rare alleles at the IL1RN and IL1L1 loci conferred a more than additive increase in the risk of disease compared to IL1RN+2018 or IL1L1+4734 alone [OR 3.37 (1.60, 7.06); P = 0.002], suggesting possible synergy between the IL1RN and IL1L1 genes. This effect was stronger in patients with severe disease (alopecia totalis/universalis) [OR 4.62 (1.87, 11.40), P = 0.0022], and in those with early age at onset (< 20 years) [OR = 6.38 (2.64, 15.42), P = 0.0002]. Our results suggest that these polymorphisms within IL1RN and IL1L1 themselves or a gene in linkage disequilibrium with IL1RN and IL1L1 predispose to the more severe forms of alopecia areata.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/IL1RN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IL36RN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin 1 Receptor Antagonist...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukins,
http://linkedlifedata.com/resource/pubmed/chemical/Sialoglycoproteins
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0960-7420
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
25-30
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pubmed:dateRevised |
2011-10-3
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pubmed:meshHeading |
pubmed-meshheading:11841485-Adult,
pubmed-meshheading:11841485-Alopecia Areata,
pubmed-meshheading:11841485-Epistasis, Genetic,
pubmed-meshheading:11841485-Female,
pubmed-meshheading:11841485-Genetic Predisposition to Disease,
pubmed-meshheading:11841485-Humans,
pubmed-meshheading:11841485-Interleukin 1 Receptor Antagonist Protein,
pubmed-meshheading:11841485-Interleukins,
pubmed-meshheading:11841485-Male,
pubmed-meshheading:11841485-Middle Aged,
pubmed-meshheading:11841485-Sequence Analysis, DNA,
pubmed-meshheading:11841485-Sequence Homology,
pubmed-meshheading:11841485-Sialoglycoproteins
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pubmed:year |
2002
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pubmed:articleTitle |
Genetic analysis of the interleukin-1 receptor antagonist and its homologue IL-1L1 in alopecia areata: strong severity association and possible gene interaction.
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pubmed:affiliation |
Division of Genomic Medicine, University of Sheffield, Royal Hallamshire Hospital, Sheffield S10 2JF, UK. r.taziahnini@sheffield.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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