NOD2/CARD15 Mutations and Presence of Granulomas in Pediatric and Adult Crohn’s Disease

Abstract

We did not find any correlation between NOD2 mutations and granuloma formation. The cause of granulomas in CD remains elusive.

Polymorphisms in the TNF-α Promoter and Variability in the Granulomatous Response in Patients with Crohn's Disease

“…The ability to use this response to contain bacteria on the "wrong side of the fence" may be modulated by an individual's genetic makeup. The NOD2/ CARD15 and TLR4 disease susceptibility genotypes have not been found to be associated with presence or absence of granulomas (22,23), raising the possibility that genes unrelated to disease susceptibility, such as those that may cause alterations in processes related to granuloma formation, may play a role. We explored the TNF-␣ promoter for a genotypic association, since TNF-␣ plays a pivotal role in both CD and in the granulomatous response, and functional polymorphisms that affect TNF-␣ are fairly common.…”

“…All pathologic specimens were reviewed for presence of epithelioid granulomas by pathologists within participating centers. Patients included in this study were from a previously published cohort, in whom we established that the presence or absence of granulomas was unrelated to the number of biopsies sampled (mean number of biopsies 10.4 Ϯ 6.2 with granulomas, versus 8.9 Ϯ 5.6 biopsies without granulomas, NS), or to NOD2/CARD15 genotype (23).…”

“…These include the NOD2/CARD15 gene, (an intracellular sensor for muramyl dipeptide) (18 -21), and toll-like receptor 4 (TLR4), which recognizes LPS (24). At present, there is no evidence of an association between NOD2/ CARD15 or TLR4 genotype, and presence of granulomas (22,23) Granulomatous diseases and CD are characterized by TNF-␣ secretion. Elevated levels of TNF-␣ are found within granuloma tissue in CD and other granulomatous diseases, and are required for granuloma integrity in animal models and human diseases (14,25,26).…”

Role of CARD15, DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases

“…Paradoxically, in contrast to the data in adults, there are studies mainly looking at CARD15 polymorphisms [11][12][13][14][15][16][17][18][19]40] , while being scarce and conflicting on OCTN1/2 and DLG5 genes [41][42][43][44] . Moreover, many pediatric series are flawed by a small sample size [11,12,15,16,18,19,43,44] , little information on UC patients [13,15,41] , and lack of control populations [11,12,16,17,19] . In this study we have investigated the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in IBD predisposition in a large Italian pediatric cohort.…”

“…CARD15 major variants are mostly associated with ileal disease and stricturing behaviour [7] . In pediatric series, a correlation with ileal localization [11][12][13][14] , stricturing behaviour [12,13,15] early surgery [12,13] growth delay [13,14] , and higher disease activity [13,16] has been reported, although with conflicting findings [17][18][19] . Functional polymorphisms in the carnitine organic cation transporter cluster (OCTN1/2) [20] on chromosome 5q31 and mutations in disc large gene 5 (DLG5) [21] on www.wjgnet.com the long arm of chromosome 10 (10q23) have also been reported to be associated with CD.…”