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 TM technology.The nonsynonymous SNP rs11209026 (Arg381Gln) in the interleukin (IL)-23 receptor (IL23R) gene was associated with chronic sarcoidosis (OR 0.63; ), which was supported by the result of a transmission disequilibrium test analysis in the independent family sample (OR 0.50; p50.031). Marker rs12035082 located at chromosome 1q24.3 was found to be associated with the acute subphenotype (OR 1.36; p56.80610 -7 ) and rs916977 (HERC2 locus; OR 1.30; p54.49610 -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.

Update in Diffuse Parenchymal Lung Disease 2011

“…Thus, in susceptible individuals, inanimate remnants of bacteria or remote infection may be capable of inducing sustained sarcoid-like inflammation (51,52). The nature of these disease susceptibilities may be queried in genome-wide association studies, which have identified a number of gene variants associated with sarcoidosis and other granulomatous disorders (53)(54)(55). Another approach is the identification of molecular signatures by systems biology approaches using peripheral blood cells or lung tissue.…”

Genetics of Sarcoidosis

“…Polymorphisms in rs11209026 can affect serum IL-17A levels in rheumatoid arthritis patients [116]. In a German cohort, rs11209026A was protective against chronic sarcoidosis [117].…”

Patterns of airway involvement in inflammatory bowel diseases

“…They both share multi-organ manifestations (joints, eye, skin). Sarcoidosis and IBD seem to share a genetic overlap regarding cytoplasmic nucleotide oligomerization domains 1 and 2 and certain polymorphisms in chromosomes 1 (loci IL-23R and 1q.24.3) and 15 (locus HERC2) [63] . IBD, as discussed earlier in this article, may exhibit granulomatous lung disease, mainly bronchiolitis.…”