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Genome‐wide association study identifies new susceptibility loci for cutaneous lupus erythematosus
Author(s) -
Kunz Manfred,
König Inke R.,
Schillert Arne,
Kruppa Jochen,
Ziegler Andreas,
Grallert Harald,
MüllerNurasyid Martina,
Lieb Wolfgang,
Franke Andre,
Ranki Annamari,
Panelius Jaana,
Koskenmies Sari,
Hasan Taina,
Kere Juha,
Rönn AnnCharlotte,
Simon Jan C.,
Schmidt Enno,
Wenzel Joerg,
Tüting Thomas,
Landsberg Jennifer,
Zeller Tanja,
Blankenberg Stefan,
Gläser Regine,
Patsinakidis Nikolaos,
Kuhn Annegret,
Ibrahim Saleh M.
Publication year - 2015
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12708
Subject(s) - single nucleotide polymorphism , immunology , major histocompatibility complex , human leukocyte antigen , biology , genetics , pathogenesis , autoimmune disease , immune system , gene , genotype , antigen , antibody
Cutaneous lupus erythematosus ( CLE ) is a chronic autoimmune disease of the skin with typical clinical manifestations. Here, we genotyped 906 600 single nucleotide polymorphisms ( SNP s) in 183 CLE cases and 1288 controls of Central European ancestry. Replication was performed for 13 SNP s 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 ( P GWAS = 1.4 × 10 −12 ), rs9267531 ( P GWAS = 4.7 × 10 −10 ), rs4410767 ( P GWAS = 1.0 × 10 −9 ) and rs3094084 ( P GWAS = 1.1 × 10 −9 ). All mentioned SNP s 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 ‐ DQA 1 ), MICA , MICB , MSH 5 , TRIM 39 and RPP 21 . For example, TRIM 39/ RPP 21 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 ‐ DQA 1 ), apoptosis regulation, RNA processing and interferon response ( MICA , MICB , MSH 5 , TRIM 39 and RPP 21 ).