Novel genetic markers in inflammatory bowel disease

Abstract

Genetic factors play a significant role in determining inflammatory bowel disease (IBD) susceptibility. Epidemiologic data support genetic contribution to the pathogenesis of IBD, which include familial aggregation, twin studies, racial and ethnic differences in disease prevalence. Linkage studies have identified several susceptibility genes contained in different genomic regions named IBD1 to IBD9. Nucleotide oligomerization domain (NOD2) and human leukocyte antigen (HLA) genes are the most extensively studied genetic regions (IBD1 and IBD3 respectively) in IBD. Mutations of the NOD2 gene are associated with Crohn's disease (CD) and several HLA genes are associated with ulcerative colitis (UC) and CD. Toll like receptors (TLRs) have an important role in the innate immune response against infections by mediating recognition of pathogen-associated microbial patterns. Studying single-nucleotide polymorphisms (SNPs) in molecules involved in bacterial recognition seems to be essential to define genetic backgrounds at risk of IBD. Recently, numerous new genes have been identified to be involved in the genetic susceptibility to IBD: NOD1/Caspase-activation recruitment domains 4 (CARD4), Chemokine ligand 20 (CCL20), IL-11, and IL-18 among others. The characterization of these novel genes potentially will lead to the identification of therapeutic agents and clinical assessment of phenotype and prognosis in patients with IBD.

Balancing inflammatory, lipid, and xenobiotic signaling pathways by VSL#3, a biotherapeutic agent, in the treatment of inflammatory bowel disease

“…41,44,46 We noted significant upregulation of IRGM and in genes associated with the biological process defined as phagocytosis, engulfment in IL10-KO mice. Recently, the notion that autophagy is stimulated by TLR pathways such as MyD88 and the recognition of conserved pathogen-associated molecular patterns (PAMPs) associated with gut microbes has been presented.…”

Muramyl dipeptide responsive pathways in Crohn’s disease: from NOD2 and beyond

“…multiprotein complexes, which are involved in the conversion of pro-caspase-1 to casapase-1 through a CARD-CARD interaction. Active caspase 1 leads to cleavage of pro-inflammatory cytokines, such as pro-IL-1β and pro-IL-18, allowing more secretion of mature IL-1β and IL-18 [134,135] (Fig. 5).…”

Cutaneous Aseptic Neutrophilic Abscesses and <i>Yersinia</i><i>enterocolitica</i> Infection in a Case Subsequently Diagnosed as Crohn’s Disease

“…Other genetic factors play a significant role in determining IBD susceptibility. From most of the genome-wide scans performed in IBD, a number of susceptibility regions on several chromosomes have been found and according to their initial date of reporting and independent confirmations, the regions on such chromosomes have been named IBD1–IBD9 (table 1) [9]. …”