Abstract |
Evidence, largely from Irish pedigrees, indicates that a susceptibility locus for psoriasis maps to chromosome 4q. The gene encoding interferon regulatory factor-2 (IRF-2) maps to this region, and, as mice lacking IRF-2 exhibit a dermatologic phenotype resembling many aspects of human psoriasis, IRF-2 represents an attractive positional candidate. We set out to establish whether variation in IRF-2 sequence or expression was related to the development of psoriasis. First, the promoter, coding, and adjacent untranslated regions of IRF-2 were screened in individuals from 4q-linked families. Neither variant identified (IVS1A+29A/G; IVS3+729T/C), however, had functional credentials or statistical evidence supporting a susceptibility role. Second, in 62 Irish parent-offspring trios ascertained for psoriasis, we conducted a linkage-disequilibrium screen of the IRF2 region using a dense microsatellite map (covering 1.5 Mb from D4S1554 to D4S1540). Though there was nominal association for D4S1554/D4S2348 haplotypes (p=0.03) with one haplotype showing particularly skewed transmission to psoriatic offspring (p=0.0002, uncorrected), these markers lie some distance (500 kb) from IRF-2. Finally, we found no abnormalities of IRF-2 protein expression or distribution in skin biopsies from psoriatic individuals. These diverse lines of inquiry allow us to exclude variation in IRF2 as responsible for the 4q-linkage signal previously identified in Irish pedigrees.
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Authors | James Parkinson, Celine Charon, Barbara S Baker, Anne V Powles, Sarah Rogers, Ann Caird, Damian Smedley, Stephanie Halford, Lionel Fry, Mark I McCarthy |
Journal | The Journal of investigative dermatology
(J Invest Dermatol)
Vol. 122
Issue 3
Pg. 640-3
(Mar 2004)
ISSN: 0022-202X [Print] United States |
PMID | 15086546
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA-Binding Proteins
- IRF2 protein, human
- Interferon Regulatory Factor-2
- Repressor Proteins
- Transcription Factors
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Topics |
- Chromosome Mapping
- Chromosomes, Human, Pair 4
- DNA-Binding Proteins
(analysis, genetics)
- Genetic Predisposition to Disease
- Humans
- Immunohistochemistry
- Interferon Regulatory Factor-2
- Linkage Disequilibrium
- Mutation
- Psoriasis
(genetics)
- Repressor Proteins
- Transcription Factors
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