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

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).

• 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
• Journal: Experimental dermatology (Exp Dermatol) Vol. 24 Issue 7 Pg. 510-5 (Jul 2015) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 25827949 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Carrier Proteins
• Cell Cycle Proteins
• HLA-DQ alpha-Chains
• HLA-DQA1 antigen
• Histocompatibility Antigens Class I
• MHC class I-related chain A
• MICB antigen
• MSH5 protein, human
• TRIM39 protein, human
• Ubiquitin-Protein Ligases
• Ribonuclease P

Topics

• Carrier Proteins (genetics)
• Case-Control Studies
• Cell Cycle Proteins (genetics)
• Chromosomes, Human, Pair 6 (genetics)
• Finland
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Germany
• HLA-DQ alpha-Chains (genetics)
• Histocompatibility Antigens Class I (genetics)
• Humans
• Lupus Erythematosus, Cutaneous (genetics, immunology)
• Major Histocompatibility Complex
• Polymorphism, Single Nucleotide
• Ribonuclease P (genetics)
• Ubiquitin-Protein Ligases