CARD15 in inflammatory bowel disease and Crohn's disease phenotypes: An association study and pooled analysis

Oostenbrug, Liekele E.; Nolte, Ilja M.; Oosterom, Elvira; Steege, Gerrit van der; Meerman, Gjt; Dullemen, Hendrik M. van; Drenth, Joost P.H.; Jong, Dirk J. de; Linde, K; Jansen, Petér L. M.; Kleibeuker, Jan H.

doi:10.1016/j.dld.2006.06.042

Cited by 29 publications

(33 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similar findings were reported in CD, where NOD2 carrier status has been associated not only with a more aggressive disease phenotype but also to an increased likelihood of steroid refractoriness and a higher need for surgery [5,9,10,[38][39][40][41][42][43][44][45][46][47][48][49].…”

Section: Discussionsupporting

confidence: 75%

“…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].…”

Section: Discussionmentioning

confidence: 99%

“…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].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

Freire

Cardoso

Figueiredo

et al. 2014

Int J Colorectal Dis

View full text Add to dashboard Cite

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

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

Freire

Cardoso

Figueiredo

et al. 2014

Int J Colorectal Dis

View full text Add to dashboard Cite

show abstract

“…On the basis of our exclusion criteria, we excluded 42 studies ( (11,12 ), the controls were in Hardy-Weinberg equilibrium.…”

Section: Resultsmentioning

confidence: 99%

Genotyping for NOD2 Genetic Variants and Crohn Disease: a Metaanalysis

2009

View full text Add to dashboard Cite

Background: Arg702Trp, Gly908Arg, and Leu1007fsinsC variants of the NOD2 gene (nucleotide-binding oligomerization domain containing 2; alias, CARD15) influence the risk of Crohn disease. Methods: We conducted a systematic review to examine whether Arg702Trp, Gly908Arg, and Leu1007fsinsC are equally important risk factors for Crohn disease. In addition, we used studies for which combined information from all genotypes was available to compare risks in simple heterozygotes, compound heterozygotes, and homozygotes. PubMed, EMBASE, and Web of Science were searched. Seventy-five articles (18 727 cases and 17 102 controls) met the inclusion criteria and contributed data to the metaanalyses. Results: The odds ratios per allele for Crohn disease were 2.2 (95% CI, 2.0–2.5) for Arg702Trp, 2.6 (2.2–2.9) for Gly908Arg, and 3.8 (3.4–4.3) for Leu1007fsinsC (z-test results: Arg702Trp vs Gly908Arg, P = 0.03; Arg702Trp vs Leu1007fsinsC, P < 0.001; Gly908Arg vs Leu1007fsinsC, P < 0.001). When all 3 genotypes were combined, odds ratios for Crohn disease were 2.4 (95% CI, 2.0–2.8) for simple heterozygotes, 9.0 (6.0–13.5) for compound heterozygotes, and 6.7 (4.1–10.9) for homozygotes, compared with noncarriers (z-test results: simple heterozygotes vs compound heterozygotes, P < 0.001; simple heterozygotes vs homozygotes, P < 0.001; compound heterozygotes vs homozygotes, P = 0.18). Conclusions: The per-allele risk of Crohn disease was markedly higher for Leu1007fsinsC than for Arg702Trp and Gly908Arg. Combining all genotypes revealed the risks of Crohn disease for compound heterozygotes and homozygotes to be similar and markedly higher than for simple heterozygotes.

show abstract

“…In support of this finding, meta-analysis data from two separate studies demonstrate that the 1007-/C mutation made the most significant contribution to increased disease susceptibility. 8,34 In addition, our previous work using TDT analysis has demonstrated in the Scottish population that only the 1007-/C mutation is significantly over transmitted from parents to children. 19 In case-control analysis in Scottish adults and children there was significantly higher mutant allele frequency in CD patients of both 1007-/C and 908G/R but no significant difference in 702R/W frequency between cases and controls.…”

Section: Regression Analysis Of CD Susceptibility Genes In Scottish Cmentioning

confidence: 99%

Detailed assessment of NOD2/CARD15 exonic variation in inflammatory bowel disease in Scotland: implications for disease pathogenesis

et al. 2008

View full text Add to dashboard Cite

The high incidence of Scottish Crohn's disease (CD) is not explained by the common three NOD2/CARD15 variants. We aimed to identify population-specific NOD2/CARD15 coding variants. A total of 1478 (320 inflammatory bowel disease patients o16 years, 343 adult CD patients, 542 parents and 273 controls). All NOD2/CARD15 exons were sequenced in 24 CD patients. Sequencing identified 18 single-nucleotide polymorphisms (SNPs) including 4 non-synonymous coding SNPs altering the structure of the Leucine-rich region-two were well established (1007-/C and 908G/R). Two other variants, valine955isoleucine (955V/I) and methionine863valine (863M/V), were genotyped in all subjects. 863M/V carriage was not significantly higher in CD patients vs controls (1.35 vs 0.37%, P ¼ 0.27). 955V/I carriage was no higher in CD or ulcerative colitis patients (12.8 and 15.8%, respectively) compared to controls (16.2%). Transmission disequilibrium test analysis was negative. 955V/I carriage was higher in indeterminate colitis patients (n ¼ 29) compared to controls (41.4 vs 16.2%, P ¼ 0.001, OR ¼ 3.6 (1.6-8.2)). Population-specific NOD2/CARD15 exonic variants do not account for the high-CD prevalence in Scotland.

show abstract

CARD15 in inflammatory bowel disease and Crohn's disease phenotypes: An association study and pooled analysis

Cited by 29 publications

References 43 publications

NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

Genotyping for NOD2 Genetic Variants and Crohn Disease: a Metaanalysis

Detailed assessment of NOD2/CARD15 exonic variation in inflammatory bowel disease in Scotland: implications for disease pathogenesis

Contact Info

Product

Resources

About