NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

Abstract

Purpose NOD2 mutations have been linked to an increased risk of Crohn's disease and to some of its phenotypes. The association between NOD2 mutations and susceptibility to ulcerative colitis (UC) remains somewhat controversial and potential correlations between these mutations and UC phenotype have not been studied. Aim To assess whether NOD2 mutations are a risk factor for UC in Portugal and if there are any genotype-phenotype correlations in these patients. Methods The three main NOD2 mutations were searched in 200 patients with UC and in 202 healthy controls. Results NOD2 mutations were present in 28 patients with UC (14.0 %) and in 27 controls (13.4 %) (p=0.853). Mutation carriers were more likely to receive steroids during the first year of disease than non-carriers (54.2 % vs. 29.6 %, p= 0.018) and among these patients the need for intravenous administration was more frequent in those with the R702W polymorphism (90.0 % vs. 45.5 %, p=0.014). In patients with severe colitis admitted for intravenous steroids, a greater proportion of mutation carriers was considered intravenous-steroid refractory and required salvage therapy (90.0 % vs. 38.1 %, p=0.004). Patients with NOD2 mutation were submitted to colectomy more frequently than non-carriers (17.9 % vs. 4.1 %. p=0.015). No correlation with the need for immunosuppressants/immunomodulators was found. Conclusions In the Portuguese population, NOD2 mutations do not increase the risk of UC but are associated with a more aggressive course including greater need of steroids in the first

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

“…These autoimmune diseases responsible genes might be critical for the development of CD. Recently, study found that CXCL5 [454], S100A12 [455], OSM (oncostatin M) [456], LRG1 [457], LCN2 [458], CXCL1 [459], S100A9 [460], IFITM1 [461], XBP1 [462], MMP3 [457], IFITM3 [463], IL1B [464], GBP5 [465], HGF (hepatocyte growth factor) [466], CXCL9 [467], SLC11A1 [468], IL1RN [469], STAT1 [470], CYP27B1 [471], MMP1 [472], SOCS3 [473], TLR8 [474], CD55 [475], CCL28 [476], FCGR2A [477], CCL2 [478], CFB (complement factor B) [479], CD14 [480], GPR84 [481], PCSK9 [482], FOXP3 [483], LPL (lipoprotein lipase) [484], IL1R2 [485], TLR2 [486], MEFV (MEFV innate immuity regulator, pyrin) [487], VWF (von Willebrand factor) [488], NOD2 [489], DMBT1 [490], HSPA6 [491], TIMP1 [492], ICAM1 [493], EGR1 [494], CCL11 [495], IFNG (interferon gamma) [496], APOE (apolipoprotein E) [497] FGR (FGR proto-oncogene, Src family tyrosine kinase) [498], IL6 [499], SPP1 [192], IL11 [500], RNF186 [501], MMP2 [502], CD24 [503], SPHK1 [504], GZMB (granzyme B) [505], MUC5AC [506], SERPINA3 [507], TWIST1 [508], PLAU (plasminogen activator, urokinase) [509], CA2 [510], CA9 [510], CTLA4 [511], PADI4 [512], MMP13 [513], MPO (myeloperoxidase) [244], LEFTY1 [514], CA1 [515], MMP7 [513], ABCG2 [516], CYP2J2 [517], AICDA (activation induced cytidine deaminase) [518], CYP2D6 [519], CYP3A5 [52...…”

Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes

“…On the other hand, association studies among Indian IBD patients have shown a weak relationship of the NOD2 gene mutations with UC, but not with CD [31]. In turn, the study of NOD2 gene variants in patients with UC in the Portuguese population did not correlate them with increased risk of the disease; however, a tendency for a more aggressive course of the disease was observed among carriers of rare NOD2 variants [32].…”

Interplay between Cellular and Molecular Mechanisms Underlying Inflammatory Bowel Diseases Development—A Focus on Ulcerative Colitis

“…Despite the fact that UC and Crohn’s disease are related pathologies, there are differences in some of the susceptibility alleles. For example, if Nod2 was one of the first genes to be associated with Crohn’s disease, only later on a studied developed by Freire et al [ 30 ] correlated the Nod2 mutations with a more aggravated condition for UC patients. Moreover, patients with Nod2 mutations have been associated with defective Atg16L1 recruitment, leading to autophagy induction [ 31 ].…”