Inflammatory Bowel Disease 29

A number sign (#) is used with this entry because of evidence that susceptibility to inflammatory bowel disease-29 (IBD29) is conferred by variation in the C1ORF106 gene (INAVA; 618051) on chromosome 1q32.

Description

Inflammatory bowel disease is a chronic inflammatory condition of the gastrointestinal tract (summary by Mohanan et al., 2018).

For a general description and a discussion of genetic heterogeneity of inflammatory bowel disease, including Crohn disease (CD) and ulcerative colitis (UC), see IBD1 (266600).

Molecular Genetics

Rivas et al. (2011) used pooled next-generation sequencing to study 56 genes from regions associated with Crohn disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in 9 independent case-control series (16,054 Crohn disease cases, 12,153 ulcerative colitis cases, and 17,575 healthy controls), they identified tyr333-to-phe (Y333F; 618051.0001) in the C1ORF106 gene as an independent risk factor for inflammatory bowel disease (p = 0.009). Mohanan et al. (2018) demonstrated that the Y333F variant decreased INAVA protein stability through ubiquitination and subsequent degradation by the proteasome, thereby impairing the turnover and degradation of cytohesin-1 (CYTH1; 182115).

Jostins et al. (2012) performed a metaanalysis of CD and UC genomewide association scans, with a combined total of more than 75,000 cases and controls, and found an association between inflammatory bowel disease and SNP (rs7554511). Yan et al. (2017) stated that this polymorphism was located in an intronic region between exons 6 and 7 of the INAVA gene. Yan et al. (2017) found that monocyte-derived macrophages (MDMs) from the rs7554511 C risk carriers expressed lower levels of INAVA and demonstrated decreased signaling, cytokine secretion, and bacterial clearance upon stimulation with ligands for a broad range of pattern recognition receptors (PRRs).