Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations

Hampe, Jochen; Cuthbert, Andrew; Croucher, Peter J.P.; Mirza, Muddassar M.; Mascheretti, Silvia; Fisher, Sheila; Frenzel, H; King, Kathy; Hasselmeyer, Anja; Macpherson, Andrew J.; Bridger, Stephen; Deventer, Sander van; Forbes, Alastair; Nikolaus, Susanna; Lennard‐Jones, J. E.; Foelsch, Ulrich R.; Krawczak, Michael; Lewis, Cathryn M.; Schreiber, Stefan; Mathew, Christopher G.

doi:10.1016/s0140-6736(00)05063-7

Cited by 984 publications

(659 citation statements)

References 27 publications

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“…A major susceptibility locus for CD is located on chromosome 16 (IBD1) 38 and mutations in the leucine-rich region (LRR) of the CARD15 (NOD2) (MIM 605956) gene associated with CD have been discovered. [39][40][41] We previously found no evidence of linkage of this locus to sarcoidosis, 42 and Schurmann et al 35 also could not find evidence that CARD15 mutations are associated with sarcoidosis. No evidence exists for a sarcoidosis susceptibility locus on chromosome 16 in the present study (Figure 1).…”

Section: Discussionmentioning

confidence: 80%

Genome-wide search for sarcoidosis susceptibility genes in African Americans

et al. 2005

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Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P ¼ 0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation.

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Section: Discussionmentioning

confidence: 80%

Genome-wide search for sarcoidosis susceptibility genes in African Americans

et al. 2005

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“…The cohorts have been used in a number of previous studies and the clinical and ethical issues of the recruitment process were reviewed as part of these publications. 19,16,24,15 An overview of the investigated sample is given in Table 1.…”

Section: Investigated Patient Samplementioning

confidence: 99%

“…10,11 Genetic linkage studies in IBD provide a thorough proof for a genetic background, 12 and the first disease gene (NOD2 or CARD15) has been identified for CD. [13][14][15][16][17] Genome-wide linkage analyses in large patient cohorts of different ethnic backgrounds have defined IBD susceptibility loci located on chromosomes 3, 6, 7, 12 and 16. 12,18-20 Recently, mutations in the murine Anterior Gradient 2 (AGR2) gene have been associated with a spontaneous phenotype characterized by diarrhea and goblet cell dysfunction resembling pathological changes seen in human UC (European patent WO2004056858).…”

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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“…[1][2][3][4] The incidence of IBD is relatively higher in Caucasian than in Asian populations; however, the incidence in Asia is increasing. 5,6 Of the two types of IBD, the genetic contribution to disease risk has been documented more extensively and clearly for CD [7][8][9][10][11][12][13][14][15][16][17] than for UC. [18][19][20][21] So far, linkage and genome-wide association studies have identified more than 30 CD-susceptibility loci in Caucasian populations.…”

Section: Introductionmentioning

confidence: 99%

No association between TNFSF15 and IL23R with ulcerative colitis in Koreans

et al. 2011

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Recent genome-wide association studies have shown that some Crohn's disease (CD)-associated loci also contribute to ulcerative colitis (UC) susceptibility. To understand the genetic relationship between the two forms of inflammatory bowel disease, we investigated the well-established CD-susceptibility genes TNFSF15 (tumor necrosis factor ligand superfamily, member 15) and IL23R in Korean patients with UC. Eight TNFSF15 and five IL23R single-nucleotide polymorphisms were genotyped in 654 patients with UC and in 601 healthy controls. There was no association between TNFSF15 or IL23R variants and UC in Korean individuals, in contrast to previous reports of a shared association of the IL23R gene with both CD and UC in Caucasian individuals. Our data suggest that neither TNFSF15 nor IL23R variants contribute to UC susceptibility in Koreans.

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Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations

Cited by 984 publications

References 27 publications

Genome-wide search for sarcoidosis susceptibility genes in African Americans

Genome-wide search for sarcoidosis susceptibility genes in African Americans

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

No association between TNFSF15 and IL23R with ulcerative colitis in Koreans

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