TY - JOUR
T1 - Association of inflammatory bowel disease risk loci with sarcoidosis, and its acute and chronic subphenotypes
AU - Fischer, A.
AU - Nothnagel, M.
AU - Franke, A.
AU - Jacobs, G.
AU - Saadati, H. R.
AU - Gaede, K. I.
AU - Rosenstiel, P.
AU - Schürmann, M.
AU - Müller-Quernheime, J.
AU - Schreiber, S.
AU - Hofmann, S.
PY - 2011/3/1
Y1 - 2011/3/1
N2 - 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. Copyright
AB - 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. Copyright
UR - http://www.scopus.com/inward/record.url?scp=79953709377&partnerID=8YFLogxK
U2 - 10.1183/09031936.00049410
DO - 10.1183/09031936.00049410
M3 - Journal articles
C2 - 20650992
AN - SCOPUS:79953709377
VL - 37
SP - 610
EP - 616
JO - European Respiratory Journal
JF - European Respiratory Journal
SN - 0903-1936
IS - 3
ER -