Evaluation of the IRF-2 gene as a candidate for PSORS3

Foerster, John; Nolte, Ilja; Schweiger, Susann; Ehlert, Claudia; Bruinenberg, Marcel; Spaar, Katja; van der Steege, Gerrit; Mulder, Marcel; Kalscheuer, Vera M.; Moser, Bettina; Kijas, Zofia; Seeman, Petra; Ständer, Markward; Sterry, Wolfram; te Meerman, Gerard

doi:10.1046/j.0022-202X.2003.22104.x

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Evaluation of the IRF-2 gene as a candidate for PSORS3

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Schweiger, Susann
Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Kalscheuer, Vera M.
Chromosome Rearrangements and Disease (Vera Kalscheuer), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

Moser, Bettina
Max Planck Society;

Kijas, Zofia
Max Planck Society;

Seeman, Petra
Max Planck Society;

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Citation

Foerster, J., Nolte, I., Schweiger, S., Ehlert, C., Bruinenberg, M., Spaar, K., et al. (2004). Evaluation of the IRF-2 gene as a candidate for PSORS3. Journal of Investigative Dermatology, 122(1), 61-64. doi:10.1046/j.0022-202X.2003.22104.x.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0010-8908-8

Abstract

Type 1 interferon can trigger flares of psoriasis. Hypersensitivity to type 1 interferon signaling causes a psoriasis-like skin disease in mice deficient for the transcription factor interferon regulatory factor 2 (IRF2). The human IRF2 gene is located at a previously identified candidate psoriasis susceptibility locus on chromosome 4q (PSORS3 at D4S1535). Therefore, we tested association of psoriasis with IRF2. We generated a sample consisting of 157 families with a total of 521 individuals. Five novel microsatellite markers were developed and typed, and complemented with three known markers to yield a set of eight markers spaced within 600 kb around the IRF2 gene, three of which are located in the gene. We detected association of IRF2 with type 1 psoriasis at two markers in the IRF2 gene. Haplotype sharing analysis confirmed association of IRF2 with type 1 psoriasis (p=0.0017; pcorr=0.03). The 921G/A SNP in exon 9 was found to obliterate a predicted exon splice enhancer in an allele-specific manner. There was a suggestive increase of homozygosity for the splicing-deficient allele in type 1 psoriasis patients. Our data identify IRF2 as a potential susceptibility gene for psoriasis.