The differential diagnosis of idiopathic inflammatory disease by colorectal biopsy

Hamilton, Stanley R.

doi:10.1007/bf01647703

Cited by 26 publications

(9 citation statements)

References 18 publications

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“…1,2 On the basis of clinical and histopathological features, IBD is categorized into two main disease entities: Crohn's disease (CD) and ulcerative colitis (UC). 3,4 Active inflammation is marked by chronic diarrhea, rectal bleeding, abdominal pain, fever, weight loss and extraintestinal manifestations, for example, arthritis, uveitis and skin lesions. IBD is a multifactorial disease caused by the interplay of genetic, environmental and immunological factors.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of AGR2 and AGR3 as candidate genes for inflammatory bowel disease

Rosenstiel²,

Huse³

et al. 2005

Genes Immun

119

117

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Linkage analyses have implicated chromosome 7p21.3 as a susceptibility region for inflammatory bowel disease (IBD). Recently, the mouse phenotype with diarrhea and goblet cell dysfunction caused by anterior gradient protein 2 dysfunction was reported (European patent WO2004056858). The genes encoding for the human homologues AGR2 and AGR3 are localized on chromosome 7p21.3. The gene structures were verified and mutation detection was performed in 47 IBD patients. A total of 30 single nucleotide polymorphisms (SNPs) were tested for association to ulcerative colitis (UC, N ¼ 317) and Crohn's disease (CD, N ¼ 631) in a German cohort and verified in a UK cohort of 384 CD and 311 UC patients. An association signal was identified in the 5 0 region of the AGR2 gene (most significant SNP hcv1702494, nominal P TDT ¼ 0.011, P case/control ¼ 0.0007, OR ¼ 1.34, combined cohort). The risk haplotype carried an odds ratio of 1.43 in the German population (P ¼ 0.002). AGR2 was downregulated in UC patients as compared to normal controls (Po0.001) and a trend toward lower expression was seen in carriers of the risk alleles. Luciferase assays of the AGR2 promoter showed regulation by the goblet cell-specific transcription factors FOXA1 and FOXA2. In summary, AGR2 represents an interesting new avenue into the etiopathophysiology of IBD and the maintenance of epithelial integrity.

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Section: Introductionmentioning

confidence: 99%

Evaluation of AGR2 and AGR3 as candidate genes for inflammatory bowel disease

Rosenstiel²,

Huse³

et al. 2005

Genes Immun

119

117

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“…These diseases are characterized by chronic relapsing inflammation of the gastrointestinal tract. 8,9 The prevalence of IBD in some western countries is as high as 0.5%. 10,11 Consistent evidence for familial clustering, 12 an increased concordance of the IBD phenotype in monozygotic twins 13,14 and consistently positive results from genetic linkage studies have repeatedly confirmed the involvement of complex genetic factors in the etiology of these conditions.…”

Section: Introductionmentioning

confidence: 99%

Haplotype structure and association to Crohn's disease of CARD15 mutations in two ethnically divergent populations

et al. 2003

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Current debate focuses on the relevance of linkage disequilibrium (LD), ethnicity and underlying haplotype structure to the search for genes involved in complex disorders. The recently described association between single nucleotide polymorphisms (SNPs) of the CARD15 (NOD2) gene and Crohn's disease (CD) in populations of north-European descent provides a test case that we have subjected to detailed SNP haplotype based analyses. We examined 23 SNPs spanning 290 kb, including CARD15, in large North-European and Korean samples of patients with Crohn's disease and normal controls. In Europeans we confirmed that the three disease-associated SNPs occur independently but share a common background haplotype. This suggests a common origin and the possibility of an undiscovered more strongly predisposing mutation. Korean CD patients present a phenotype identical to the European patients and have not previously been screened for CARD15. The three disease-associated SNPs were absent and there was no evidence of association between CARD15 and CD. Consequently, the diseaseassociated mutations in the Europeans, which are rare, have arisen recently (after the Asian -European split). Our results highlight important issues relevant to mapping the genes that predispose to complex disorders. First, although ethnically divergent populations may present identical phenotypes they do not necessarily share the same set of predisposing genes. Second, although single-locus tests of association showed consistent association with markers throughout the gene, pair-wise LD between markers (r 2 and D') yielded very little information about actual disease-association. Third, a population comparative approach allowed refining of the marker set through the examination of shared polymorphisms and common LD-groups. This approach, in conjunction with the examination of the mutational steps in a haplotype network, allows unambiguous identification of the potentially causative mutations.

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“…The disease is clinically characterized by abdominal pain, chronic diarrhea, rectal bleeding, weight loss, intestinal stenoses, fistulae (3,4), toxic megacolon, and associated extraintestinal manifestations (5) such as arthritis and uveitis (6). On the basis of clinical and histopathological features, IBD is categorized into two main subtypes, Crohn's disease (CD; MIM 266600) and ulcerative colitis (UC; MIM 191390) (6,7).…”

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confidence: 99%

Evidence for a NOD2 -independent susceptibility locus for inflammatory bowel disease on chromosome 16p

Hampe

Frenzel

Mirza

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

101

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Heritable predisposition to inflammatory bowel disease (IBD) has been demonstrated by epidemiological and genetic analysis. Linkage of IBD to broad regions of chromosome 16 has been established by analysis of multiple populations. NOD2, located on proximal 16q, was recently identified as an IBD gene. As the linkage regions on chromosome 16 are large, we have investigated the possibility that NOD2 is not the only IBD gene located on this chromosome. A high-density experiment using 39 microsatellite markers was performed to identify additional regions of association, and to indicate areas of interest for further investigation. A triple-peaked configuration of the linkage curve with peak logarithm of odds (lod) scores of 2.7, 3.2, and 3.1 was observed on proximal 16p, proximal 16q, and central 16q, respectively. The cohort was stratified by coding individuals carrying the NOD2 single nucleotide polymorphism (SNP)8 and SNP13 ''unknown.'' Significance at the central peak, corresponding to the genomic location of NOD2, then decreased from 3.2 to 1.2. The maximal lod scores on the proximal p-arm (lod ‫؍‬ 2.1) and central q-arm (lod ‫؍‬ 2.6) changed only moderately. An exploratory association analysis (TRANSMIT) yielded a strong lead at D16S3068 (P ‫؍‬ 0.00028). The region around this marker was further investigated by using anonymous SNPs. An associated haplotype containing three SNPs was identified (peak significance P ‫؍‬ 0.00027, IBD phenotype). On stratification based on NOD2 genotype, this significance increased to P ‫؍‬ 0.0001. These results confirm the importance of NOD2 and provide evidence for a second IBD gene located on chromosome 16p.

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The differential diagnosis of idiopathic inflammatory disease by colorectal biopsy

Cited by 26 publications

References 18 publications

Evaluation of AGR2 and AGR3 as candidate genes for inflammatory bowel disease

Evaluation of AGR2 and AGR3 as candidate genes for inflammatory bowel disease

Haplotype structure and association to Crohn's disease of CARD15 mutations in two ethnically divergent populations

Evidence for a NOD2 -independent susceptibility locus for inflammatory bowel disease on chromosome 16p

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