Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease

Abstract

In this description of a genotype/phenotype correlation in CD patients and NOD2 variants, data suggest that variation in this gene contributes to the occurrence of fibrostenotic CD of the small bowel.

NOD2/CARD15, TLR4 and CD14 mutations in Scottish and Irish Crohn's disease patients: evidence for genetic heterogeneity within Europe?

“…9-12,22,23, 25 The latter observation is strongest in patients with two variant alleles, consistent with the data of Lesage et al 12 We have also seen a relatively weak association with perforating disease at diagnosis, but could not confirm the association with fibrostenosing disease. 8 We observed an association with IBD-associated peripheral arthritis; however, significance was not achieved following correction for multiple variables. It remains to be seen whether these findings will be replicated in detailed genotype-phenotype analysis in other populations.…”

“…This demonstrates that the common NOD2/CARD15 variants are significantly less common in Scottish CD than in documented populations from North America (Po0.00001), 8 Europe (Po0.00001) 7 and the United Kingdom (P ¼ 0.0012) 11 (Table 4). When compared with a population from Northern Europe, 22 these differences were not seen.…”

“…The contribution of the gene has been studied in many diverse populations, [7][8][9][10][11] with positive associations in up to 50% of CD patients. 12 However, data from Japanese, Korean and African-American individuals have not shown an association, [13][14][15] and there are now clear differences between Ashkenazi Jewish and nonJewish populations.…”

NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

“…In the past two decades, genetic variants identified as being [54,59] b No response to intravenous steroids and required salvage therapy with cyclosporine, infliximab, or colectomy c No response to cyclosporine and/or infliximab and required salvage colectomy associated with increased susceptibility to IBD were then subject to research in order to investigate whether they are also correlated with the disease phenotype. NOD2, the first gene linked with increased susceptibility to CD, has later been shown to be associated with ileal disease, early age of onset, stricturing, and/or penetrating phenotype and increased need for surgery [5,9,10,[38][39][40][41][42][43][44][45][46][47][48][49]. Among the UC susceptibility genes, HLA DRB1*0103 and the multidrug resistance gene 1 (MDR1/ABCB1) were also identified as being associated with extensive and severe disease [17,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37].…”

“…Among the UC susceptibility genes, HLA DRB1*0103 and the multidrug resistance gene 1 (MDR1/ABCB1) also contribute to clinical phenotype and natural history, being associated with extensive and severe disease [17,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. In CD, NOD2 gene mutations have repeatedly been shown to be associated with ileal disease, early age of onset, stricturing, and/or penetrating phenotype and increased need for surgery [5,9,10,[38][39][40][41][42][43][44][45][46][47][48][49]. Surprisingly, there are no studies focusing on potential genotype-phenotype associations between NOD2 mutations and UC, perhaps because it is not commonly considered a susceptibility gene for UC [5,10,50].…”