Genes and immunity, 2009-04, Vol.10 (3), p.201-209
2009
Details
- Autor(en) / Beteiligte
- Titel
- Genome-wide association scan yields new insights into the immunopathogenesis of psoriasis
- Ist Teil von
- Genes and immunity, 2009-04, Vol.10 (3), p.201-209
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Psoriasis is a common, immunologically mediated, inflammatory and hyperproliferative disease of the skin and joints, with a multifactorial genetic basis. We earlier mapped PSORS1, the major psoriasis susceptibility gene in the major histocompatibility complex (MHC), to within or very near HLA-Cw6. In an effort to identify non-MHC psoriasis genes, we carried out a collaborative genome-wide association study. After the initial follow-up genotyping of 21 single nucleotide polymorphisms from 18 loci, showing strong evidence of association in the initial scan, we confirmed evidence of association at seven loci. Three of these loci confirm earlier reports of association (HLA-C, IL12B, IL23R) and four identify novel signals located near plausible candidate genes (IL23A, IL4/IL13, TNFAIP3 and TNIP1). In other work, we have also shown that interferon-gamma (IFN-gamma) treatment induces interleukin (IL)-23 mRNA and protein in antigen-presenting cells (APC), leading to the proliferation of CD4+ and CD8+ memory T cells expressing IL-17. Although functional variants remain to be identified, we speculate that genetic variants at the IL4/IL13 locus contribute to the Th1 bias that is characteristic of psoriasis, that Th1-derived IFN-gamma supports expansion of IL-17+ T cells through APC-derived IL-23 and that negative regulation of inflammatory signaling through the NF-kappaB axis is impaired because of genetic variants of TNFAIP3 and TNIP1.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1466-4879eISSN: 1476-5470DOI: 10.1038/gene.2009.11Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2683580
- Format
- –
- Schlagworte
- Antigen-presenting cells, Antigen-Presenting Cells - immunology, Antigen-Presenting Cells - metabolism, Antigens, Arthritis, Care and treatment, CD4 antigen, CD8 antigen, Cell proliferation, Collaboration, Cytokines, Dermatology, Epidemiology, Genes, Genetic aspects, Genetic diversity, Genetic Predisposition to Disease, Genome-wide association studies, Genome-Wide Association Study, Genomes, Genotyping, Health aspects, Histocompatibility antigen HLA, Human genetics, Humans, Hyperplasia, Immunological memory, Immunopathogenesis, Interferon-gamma - genetics, Interferon-gamma - immunology, Interferon-gamma - metabolism, Interleukin 1, Interleukin 13, Interleukin 17, Interleukin 23, Interleukin 4, Interleukin-13 - genetics, Interleukin-13 - immunology, Interleukin-13 - metabolism, Interleukin-17 - genetics, Interleukin-17 - immunology, Interleukin-17 - metabolism, Interleukin-23 - genetics, Interleukin-23 - immunology, Interleukin-23 - metabolism, Interleukin-4 - genetics, Interleukin-4 - immunology, Interleukin-4 - metabolism, Interleukins, Joint diseases, Lymphocytes, Lymphocytes T, Major histocompatibility complex, Memory cells, mRNA, NF-kappa B - genetics, NF-kappa B - immunology, NF-kappa B - metabolism, NF-κB protein, Polymorphism, Single Nucleotide, Psoriasis, Psoriasis - genetics, Psoriasis - immunology, Psoriasis - metabolism, Signal Transduction - immunology, Single nucleotide polymorphisms, Single-nucleotide polymorphism, Skin diseases, T-Lymphocytes, Helper-Inducer - immunology, T-Lymphocytes, Helper-Inducer - metabolism, γ-Interferon