title: Association of inflammatory bowel disease risk loci with sarcoidosis, and its acute and chronic subphenotypes.
abstract: Sarcoidosis is a complex granulomatous inflammatory disorder that shares several clinical and pathogenic features with inflammatory bowel disease (IBD). Postulating a common genetic basis of inflammatory diseases, we tested 106 single-nucleotide polymorphisms (SNPs) that are known or have been suggested to be associated with IBD for a potential association with sarcoidosis and its acute and chronic subphenotypes. We genotyped 1,996 German sarcoidosis patients, comprising 648 acutely and 1,161 chronically affected individuals, 2,622 control subjects, and 342 German trios with affected offspring using SNPlex™ technology. The nonsynonymous SNP rs11209026 (Arg381Gln) in the interleukin (IL)-23 receptor (IL23R) gene was associated with chronic sarcoidosis (OR 0.63; p = 5.58×10(-5)), which was supported by the result of a transmission disequilibrium test analysis in the independent family sample (OR 0.50; p = 0.031). Marker rs12035082 located at chromosome 1q24.3 was found to be associated with the acute subphenotype (OR 1.36; p = 6.80×10(-7)) and rs916977 (HERC2 locus; OR 1.30; p = 4.49×10(-5)) was associated with sarcoidosis. Our results highlight the potential importance of the IL-23 signalling pathway for the development of chronic sarcoidosis. The finding links sarcoidosis pathogenesis to other inflammatory conditions and may contribute to new hypotheses on disease mechanisms.
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts University, Schittenhelmstraße 12, Kiel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Nothnagel
authors.forename: A
authors.initials: A
authors.lastname: Franke
authors.forename: G
authors.initials: G
authors.lastname: Jacobs
authors.forename: H R
authors.initials: HR
authors.lastname: Saadati
authors.forename: K I
authors.initials: KI
authors.lastname: Gaede
authors.forename: P
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: M
authors.initials: M
authors.lastname: Schürmann
authors.forename: J
authors.initials: J
authors.lastname: Müller-Quernheim
authors.forename: S
authors.initials: S
authors.lastname: Schreiber
authors.forename: S
authors.initials: S
authors.lastname: Hofmann
mesh_terms: D016022:Case-Control Studies; D005786:Gene Expression Regulation; D005819:Genetic Markers; D005838:Genotype; D005858:Germany; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000175:diagnosis*; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011786:Quality Control; D018123:Receptors, Interleukin / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012507:Sarcoidosis / Q000150:complications / Q000175:diagnosis*; D044767:Ubiquitin-Protein Ligases
chemical_list: D005819:Genetic Markers; D020662:Guanine Nucleotide Exchange Factors; C515500:IL23R protein, human; D018123:Receptors, Interleukin; C118566:HERC2 protein, human; D044767:Ubiquitin-Protein Ligases