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

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

    Research output: Contribution to journalArticle

    28 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)61-64
    Number of pages4
    JournalJournal of Investigative Dermatology
    Volume122
    Issue number1
    DOIs
    Publication statusPublished - Jan 2004

    Fingerprint

    Interferon Regulatory Factor-2
    Psoriasis
    Genes
    Interferon Type I
    Exons
    Alleles
    Chromosomes
    Microsatellite Repeats
    Skin Diseases
    Skin
    Haplotypes
    Transcription Factors
    Single Nucleotide Polymorphism
    Hypersensitivity

    Keywords

    • Psoriasis
    • DNA-binding proteins genetics
    • Psoriasis genetics
    • Repressor proteins
    • Transcription factors

    Cite this

    Foerster, J., Nolte, I., Schweiger, S., Ehlert, C., Bruinenberg, M., Spaar, K., ... te Meerman, G. (2004). Evaluation of the IRF-2 gene as a candidate for PSORS3. Journal of Investigative Dermatology, 122(1), 61-64. https://doi.org/10.1046/j.0022-202X.2003.22104.x
    Foerster, John ; Nolte, Ilja ; Schweiger, Susann ; Ehlert, Claudia ; Bruinenberg, Marcel ; Spaar, Katja ; van der Steege, Gerrit ; Mulder, Marcel ; Kalscheuer, Vera ; Moser, Bettina ; Kijas, Zofia ; Seeman, Petra ; Stander, Markward ; Sterry, Wolfram ; te Meerman, Gerard. / Evaluation of the IRF-2 gene as a candidate for PSORS3. In: Journal of Investigative Dermatology. 2004 ; Vol. 122, No. 1. pp. 61-64.
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    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.",
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    Foerster, J, Nolte, I, Schweiger, S, Ehlert, C, Bruinenberg, M, Spaar, K, van der Steege, G, Mulder, M, Kalscheuer, V, Moser, B, Kijas, Z, Seeman, P, Stander, M, Sterry, W & te Meerman, G 2004, 'Evaluation of the IRF-2 gene as a candidate for PSORS3', Journal of Investigative Dermatology, vol. 122, no. 1, pp. 61-64. https://doi.org/10.1046/j.0022-202X.2003.22104.x

    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; Moser, Bettina; Kijas, Zofia; Seeman, Petra; Stander, Markward; Sterry, Wolfram; te Meerman, Gerard.

    In: Journal of Investigative Dermatology, Vol. 122, No. 1, 01.2004, p. 61-64.

    Research output: Contribution to journalArticle

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    AU - Foerster, John

    AU - Nolte, Ilja

    AU - Schweiger, Susann

    AU - Ehlert, Claudia

    AU - Bruinenberg, Marcel

    AU - Spaar, Katja

    AU - van der Steege, Gerrit

    AU - Mulder, Marcel

    AU - Kalscheuer, Vera

    AU - Moser, Bettina

    AU - Kijas, Zofia

    AU - Seeman, Petra

    AU - Stander, Markward

    AU - Sterry, Wolfram

    AU - te Meerman, Gerard

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    N2 - 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.

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    KW - DNA-binding proteins genetics

    KW - Psoriasis genetics

    KW - Repressor proteins

    KW - Transcription factors

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