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Exp Dermatol. 2015 Jul;24(7):510-5. doi: 10.1111/exd.12708. Epub 2015 May 4.

Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus.

Author information

1
Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany.
2
Institut für Medizinische Biometrie und Statistik, und Zentrum für Klinische Studien, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany.
3
Research unit of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
4
German Center for Diabetes Research, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
5
Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
6
Department of Medicine I, Ludwig Maximilian University Munich, Munich, Germany.
7
German Center for Cardiovascular Research, Munich Heart Alliance, Munich, Germany.
8
Institute for Epidemiology and Biobank popgen, Christian-Albrechts-University of Kiel, Kiel, Germany.
9
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
10
Department of Dermatology and Allergology, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland.
11
Department of Dermatology, Tampere University Central Hospital, University of Tampere, Tampere, Finland.
12
Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden.
13
Department of Medical Genetics, Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland.
14
Clinical Research Center, Karolinska University Hospital, Huddinge, Sweden.
15
Department of Dermatology, Allergology and Venereology, University of Schleswig-Holstein, Lübeck, Germany.
16
Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
17
University Heart Center Hamburg, Clinic for General and Interventional Cardiology, German Center for Cardiovascular Research (DZHK), Hamburg, Germany.
18
Department of Dermatology and Allergology, University of Schleswig-Holstein, Kiel, Germany.
19
Department of Dermatology, Venereology and Allergology, Ruhr-University of Bochum, Bochum, Germany.
20
Division of Immunogenetics, German Cancer Research Center, Heidelberg, Germany.

Abstract

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune disease of the skin with typical clinical manifestations. Here, we genotyped 906 600 single nucleotide polymorphisms (SNPs) in 183 CLE cases and 1288 controls of Central European ancestry. Replication was performed for 13 SNPs in 219 case subjects and 262 controls from Finland. Association was particularly pronounced at 4 loci, all with genomewide significance (P < 5 × 10(-8) ): rs2187668 (PGWAS  = 1.4 × 10(-12) ), rs9267531 (PGWAS  = 4.7 × 10(-10) ), rs4410767 (PGWAS  = 1.0 × 10(-9) ) and rs3094084 (PGWAS  = 1.1 × 10(-9) ). All mentioned SNPs are located within the major histocompatibility complex (MHC) region of chromosome 6 and near genes of known immune functions or associations with other autoimmune diseases such as HLA-DQ alpha chain 1 (HLA-DQA1), MICA, MICB, MSH5, TRIM39 and RPP21. For example, TRIM39/RPP21 read through transcript is a known mediator of the interferon response, a central pathway involved in the pathogenesis of CLE and systemic lupus erythematosus (SLE). Taken together, this genomewide analysis of disease association of CLE identified candidate genes and genomic regions that may contribute to pathogenic mechanisms in CLE via dysregulated antigen presentation (HLA-DQA1), apoptosis regulation, RNA processing and interferon response (MICA, MICB, MSH5, TRIM39 and RPP21).

KEYWORDS:

autoimmune diseases; genetics; lupus; single nucleotide polymorphisms

PMID:
25827949
DOI:
10.1111/exd.12708
[Indexed for MEDLINE]

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