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Characterization of Psoriasis Susceptibility Locus 6 (PSORS6) in Patients with Early Onset Psoriasis and Evidence for Interaction with PSORS1
  1. Ulrike Hüffmeier (uhueffm{at}humgenet.uni-erlangen.de)
  1. Institute of Human Genetics, University Erlangen-Nuremberg, Germany
    1. Jesús Lascorz
    1. Institute of Human Genetics, University Erlangen-Nuremberg, Germany
      1. Tim Becker
      1. Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Germany
        1. Funda Schürmeier-Horst
        1. Department of Dermatology, University of Münster, Germany
          1. Achim Magener
          1. Department of Pathology, University of Erlangen, Germany
            1. Arif B Ekici
            1. Institute of Human Genetics, University Erlangen-Nuremberg, Germany
              1. Sabine Endele
              1. Institute of Human Genetics, University Erlangen-Nuremberg, Germany
                1. Christian T Thiel
                1. Institute of Human Genetics, University Erlangen-Nuremberg, Germany
                  1. Sybille Thoma-Uszynski
                  1. Department of Dermatology, University of Erlangen, Germany
                    1. Rotraut Mössner
                    1. Department of Dermatology, University of Göttingen, Germany
                      1. Kristian Reich
                      1. Dermatologikum Hamburg, Germany
                        1. Werner Kurrat
                        1. Asklepios Nordseeklinik, Westerland/ Sylt, Germany
                          1. Thomas F Wienker
                          1. Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Germany
                            1. Heiko Traupe
                            1. Department of Dermatology, University of Erlangen, Germany
                              1. André Reis (reis{at}humgenet.uni-erlangen.de)
                              1. Institute of Human Genetics, University Erlangen-Nuremberg, Germany

                                Abstract

                                Psoriasis is a genetically complex, chronic inflammatory skin disease. We have previously identified a susceptibility locus on chromosome 19p13 (PSORS6). In a follow-up linkage disequilibrium (LD) study in an independent family based cohort, we found evidence for association to a newly discovered microsatellite at this locus (D19SPS21, p < 5.3*10-5). An LD-based association scan in 300 trios revealed association to several single SNPs in one LD block. When we stratified this cohort for carrying the PSORS1 risk allele at the HLA-C locus, evidence for association became much stronger at single SNP and haplotype levels (p-values between 1.0*10-4 and 8.0*10-4). In a replication study of 1,114 patients and 937 control individuals, evidence for association was also observed after stratification to the PSORS1 risk allele. In both study groups, logistic regression showed evidence for interaction between the risk alleles at PSORS1 and PSORS6. Best p-values for rs12459358 in both study groups remained significant after correction for multiple testing. The associated LD block did not comprise any known genes. Interestingly, an adjacent gene, MUC16, coding for a large glycosylated protein expressed in epithelia and of unknown function, could be shown to be also expressed in tissues relevant for pathogenesis of psoriasis such as skin and thymus. Immunohistochemical analyses of skin revealed focal staining for MUC16 in suprabasal epidermal cells. Further functional studies are required to clarify its potential role in psoriasis and identify the causal variant(s) at this locus. Our data establish PSORS6 as a confirmed psoriasis susceptibility locus showing interaction with PSORS1.

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