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

Authors:
Manfred Kunz, Inke R König, Arne Schillert, Jochen Kruppa, Andreas Ziegler, Harald Grallert, Martina Müller-Nurasyid, Wolfgang Lieb, Andre Franke, Annamari Ranki, Jaana Panelius, Sari Koskenmies, Taina Hasan, Juha Kere, Ann-Charlotte Rönn, Jan C Simon, Enno Schmidt, Joerg Wenzel, Thomas Tüting, Jennifer Landsberg, Tanja Zeller, Stefan Blankenberg, Regine Gläser, Nikolaos Patsinakidis, Annegret Kuhn, Saleh M Ibrahim
Year of publication:
2015
Volume:
-
Issue:
-
Issn:
0906-6705
Journal title abbreviated:
EXP DERMATOL
Journal title long:
Experimental dermatology
Impact factor:
2.675
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 genome-wide significance (P ≤ 5 x 10(-8) ): rs2187668 (PGWAS = 1.4 x 10(-12) ); rs9267531 (PGWAS = 4.7 x 10(-10) ); rs4410767 (PGWAS = 1.0 x 10(-9) ); rs3094084 (PGWAS = 1.1 x 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 (HLADQA1), MICA, MICB, MSH5, TRIM39, and RPP21. E.g., TRIM39-RPP21 read through transcript is known mediator of the interferon response, a central pathway involved in the pathogenesis of CLE and systemic lupus erythematosus (SLE). Taken together, this genome-wide analysis of disease-association of CLE identified candidate genes and genomic regions that may contribute to pathogenic mechanisms in CLE via dysregulated antigen presentation (HLADQA1), apoptosis regulation, RNA processing and interferon response (MICA, MICB, MSH5, TRIM39, RPP21). This article is protected by copyright. All rights reserved.