Analysis of Australian Crohn's disease pedigrees refines the localization for susceptibility to inflammatory bowel disease on chromosome 16

Cavanaugh, Juleen A.; Callen, David F.; Wilson, Susan R.; Stanford, Prudence M.; Sraml, M; Górska, M; Crawford, Joanna; Whitmore, Scott A.; Shlegel, C.; Foote, Simon J.; Kohonen‐Corish, Maija; Pavli, Paul

doi:10.1046/j.1469-1809.1998.6240291.x

Cited by 99 publications

(30 citation statements)

References 25 publications

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“…The genetic component appears to play a more important role in the pathogenesis of CD than in UC [Tysk et al, 1988;Thompson et al, 1996]. Genome wide screening identified the IBD1 susceptibility locus on the pericentromeric region of chromosome 16 [Hugot et al, 1996], which has been replicated in several independent populations [Ohmen et al, 1996;Cavanaugh et al, 1998;Cho et al, 1998;Curran et al, 1998;Annese et al, 1999]. Recently, two independent groups identified Caspase Activating Recruitment Domain (CARD15), previously reported as NOD2, as the gene conferring susceptibility of CD in the IBD1 locus [Hugot et al, 2001;Ogura et al, 2001a].…”

Section: Introductionmentioning

confidence: 95%

Association between mutations in the CARD15 (NOD2) gene and Crohn's disease in Israeli Jewish patients

Fidder

Olschwang

Avidan

et al. 2003

American J of Med Genetics Pt A

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Ulcerative colitis (UC) and Crohn's disease (CD) are heterogeneous disorders characterized by chronic intestinal inflammation. Genetic predisposition is a major risk factor in both diseases. The CARD15 (NOD2) gene has been implied as a candidate gene in the pathogenesis CD. Our aim was to delineate the frequency of three missense and one frameshift variant of CARD15 in Israeli Jewish CD and UC patients. DNA was extracted from blood samples from 238 unrelated inflammatory bowel disease (IBD) patients, 68 with UC and 170 with CD. The DNA was genotyped for two missense mutations, R675W and G881R, and one frameshift mutation, 980FS981X. Mutations in CARD15 were observed with significantly greater frequency in CD patients (46/170, 27%) than in UC patients (7/68, 10%) (P = 0.005). Homozygous and compound heterozygous carriers were restricted to seven (4%) patients with CD as compared to none of the UC patients (P = 0.01). Similar rates in Ashkenazi and non-Ashkenazi Jewish patients were observed. Age-of-onset of disease was lower in Ashkenazi mutation carriers as compared to non-carriers of Ashkenazi origin (18.7 +/- 8.6 years vs. 25.8 +/- 13.4 years, respectively, P = 0.03). No other phenotypic characteristics could distinguish mutation carriers from non-carriers. We conclude that germline mutations in the CARD15 gene are more frequently found in CD than UC patients and appear to predict an earlier age-of-onset in Ashkenazi Jewish patients. No association could be demonstrated between CARD15 mutations and specific disease course or behavior.

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Section: Introductionmentioning

confidence: 95%

Association between mutations in the CARD15 (NOD2) gene and Crohn's disease in Israeli Jewish patients

Fidder

Olschwang

Avidan

et al. 2003

American J of Med Genetics Pt A

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“…Thus far, the chromosome 16 and 12 loci have demonstrated significant and confirmed evidence for linkage, with multiple other loci demonstrating suggestive evidence. The chromosome 16 locus has been confirmed extensively for CD [22][23][24][25]; only one study has demonstrated linkage in pure UC families [26]. No studies have demonstrated linkage in mixed CD-UC pairs.…”

Section: A Complex Genetic Disordermentioning

confidence: 93%

Genetic aspects of inflammatory bowel disease: How far have we come, and where are we heading?

Cho

1999

Curr Gastroenterol Rep

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Crohn"s disease and ulcerative colitis are related complex genetic disorders, with gene-gene and gene-environment interactions that are critical to their pathogenesis. Multiple genetic loci have been implicated through genome-wide searches. Of these, a locus on Crohn"s disease has been definitively established in the pericentromeric region of chromosome 16. Multiple candidate gene studies have been forwarded, and functionally significant variants in immune-associated genes will provide additional insight. Characterization of the genetic variation responsible for causing inflammatory bowel disease will result in development of novel therapeutic approaches as well as in tailoring of specific therapies to individual patients based on their specific molecular pathogenesis.

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“…Ein wesentlicher Hinweis auf die Existenz des ersten Krankheitsgens waren Kopplungsstudien [50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,68]. An betroffenen Geschwisterpaare hatte sich so bereits 1996 ein Hinweis auf eine genetische Risikoregion auf Chromosom 16 ergeben.…”

Section: Weiteres Genetisches Risikounclassified

Genetik und Umwelt

Schreiber¹,

Hampe²,

Grebe³

et al. 2002

Der Internist

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Analysis of Australian Crohn's disease pedigrees refines the localization for susceptibility to inflammatory bowel disease on chromosome 16

Cited by 99 publications

References 25 publications

Association between mutations in the CARD15 (NOD2) gene and Crohn's disease in Israeli Jewish patients

Association between mutations in the CARD15 (NOD2) gene and Crohn's disease in Israeli Jewish patients

Genetic aspects of inflammatory bowel disease: How far have we come, and where are we heading?

Genetik und Umwelt

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