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

Manfred Kunz, Inke R. Konig, Arne Schillert, Jochen Kruppa, Andreas Ziegler, Harald Grallert, Martina Muller-Nurasyid, Wolfgang Lieb, Andre Franke, Annamari Ranki, Jaana Panelius, Sari Koskenmies, Taina Hasan, Juha Kere, Ann Charlotte Ronn, Jan C. Simon, Enno Schmidt, Joerg Wenzel, Thomas Tuting, Jennifer LandsbergTanja Zeller, Stefan Blankenberg, Regine Glaser, Nikolaos Patsinakidis, Annegret Kuhn, Saleh M. Ibrahim

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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).

Original languageBritish English
Pages (from-to)510-515
Number of pages6
JournalExperimental Dermatology
Volume24
Issue number7
DOIs
StatePublished - 1 Jul 2015

Keywords

  • Autoimmune diseases
  • Genetics
  • Lupus
  • Single nucleotide polymorphisms

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