title: Variation at the IRF2 gene and susceptibility to psoriasis in chromosome 4q-linked families.
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.
authors.affiliation: Division of Medicine & Imperial College Genetics and Genomics Research Institute, Imperial College, London, UK.
authors.forename: James
authors.initials: J
authors.lastname: Parkinson
authors.forename: Celine
authors.initials: C
authors.lastname: Charon
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Baker
authors.forename: Anne V
authors.initials: AV
authors.lastname: Powles
authors.forename: Sarah
authors.initials: S
authors.lastname: Rogers
authors.forename: Ann
authors.initials: A
authors.lastname: Caird
authors.forename: Damian
authors.initials: D
authors.lastname: Smedley
authors.forename: Stephanie
authors.initials: S
authors.lastname: Halford
authors.forename: Lionel
authors.initials: L
authors.lastname: Fry
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
mesh_terms: D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D050836:Interferon Regulatory Factor-2; D015810:Linkage Disequilibrium; D009154:Mutation; D011565:Psoriasis / Q000235:genetics*; D012097:Repressor Proteins; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; D012097:Repressor Proteins; D014157:Transcription Factors