Extreme heterogeneity in CARD15 and DLG5 Crohn disease-associated polymorphisms between German and Norwegian populations

Valentina Medici, Silvia Mascheretti, Peter J P Croucher, Monika Stoll, Jochen Hampe, Jochen Grebe, Giacomo C. Sturniolo, Camilla Solberg, Jorgen Jahnsen, Bjorn Moum, Stefan Schreiber, Morten H. Vatn

Research output: Contribution to journalArticle

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Abstract

The first gene associated with Crohn disease (CD) has been identified as CARD15 (16q12). Three variants, R702W, G908R and 1007fsinsC are strongly and independently associated with the disease. A second gene, conveying a smaller risk for inflammatory bowel disease (IBD), has been identified as DLG5 (10q23). We assess the frequency of the CARD15 SNPs and of the R30Q mutation in DLG5 and their contribution to the development of CD in a cohort of unrelated IBD patients (151 CD, 325 ulcerative colitis (UC)) and healthy controls (236) from South-east Norway (IBSEN cohort). Genotype-based tests of population differentiation using 23 SNPs across CARD15, together with estimates of FST, indicated that the German and Norwegian background populations could be differentiated at the CARD15 locus. The Norwegian and German CD samples exhibited particularly strong differentiation at the three predisposing loci and those marking their background haplotype. There were significantly lower frequencies of the CARD15 SNPs and no significant association with CD in the Norwegian samples. Only a marginal association was observed for the subphenotypes ileitis and ileocolitis vs colitis (P=0.048). The population attributable risk percentage (PAR%) for CARD15 variants in the Norwegian cohort is the lowest reported for a European population (1.88%), except Iceland. Similarly, the DLG5 variant showed no association with CD or IBD, however, there was a negative correlation with stricture (P=0.035). The present results are consistent with an emerging pattern of a low frequency of the CARD15 variants in Northern countries where the prevalence of IBD is greatest.

Original languageEnglish (US)
Pages (from-to)459-468
Number of pages10
JournalEuropean Journal of Human Genetics
Volume14
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Fingerprint

Crohn Disease
Inflammatory Bowel Diseases
Population
Single Nucleotide Polymorphism
Ileitis
Iceland
Colitis
Norway
Ulcerative Colitis
Haplotypes
Genes
Pathologic Constriction
Genotype
Mutation

Keywords

  • CARD15
  • Crohn disease
  • DLG5
  • NOD2
  • Norway
  • Ulcerative colitis

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Extreme heterogeneity in CARD15 and DLG5 Crohn disease-associated polymorphisms between German and Norwegian populations. / Medici, Valentina; Mascheretti, Silvia; Croucher, Peter J P; Stoll, Monika; Hampe, Jochen; Grebe, Jochen; Sturniolo, Giacomo C.; Solberg, Camilla; Jahnsen, Jorgen; Moum, Bjorn; Schreiber, Stefan; Vatn, Morten H.

In: European Journal of Human Genetics, Vol. 14, No. 4, 04.2006, p. 459-468.

Research output: Contribution to journalArticle

Medici, V, Mascheretti, S, Croucher, PJP, Stoll, M, Hampe, J, Grebe, J, Sturniolo, GC, Solberg, C, Jahnsen, J, Moum, B, Schreiber, S & Vatn, MH 2006, 'Extreme heterogeneity in CARD15 and DLG5 Crohn disease-associated polymorphisms between German and Norwegian populations', European Journal of Human Genetics, vol. 14, no. 4, pp. 459-468. https://doi.org/10.1038/sj.ejhg.5201576
Medici, Valentina ; Mascheretti, Silvia ; Croucher, Peter J P ; Stoll, Monika ; Hampe, Jochen ; Grebe, Jochen ; Sturniolo, Giacomo C. ; Solberg, Camilla ; Jahnsen, Jorgen ; Moum, Bjorn ; Schreiber, Stefan ; Vatn, Morten H. / Extreme heterogeneity in CARD15 and DLG5 Crohn disease-associated polymorphisms between German and Norwegian populations. In: European Journal of Human Genetics. 2006 ; Vol. 14, No. 4. pp. 459-468.
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abstract = "The first gene associated with Crohn disease (CD) has been identified as CARD15 (16q12). Three variants, R702W, G908R and 1007fsinsC are strongly and independently associated with the disease. A second gene, conveying a smaller risk for inflammatory bowel disease (IBD), has been identified as DLG5 (10q23). We assess the frequency of the CARD15 SNPs and of the R30Q mutation in DLG5 and their contribution to the development of CD in a cohort of unrelated IBD patients (151 CD, 325 ulcerative colitis (UC)) and healthy controls (236) from South-east Norway (IBSEN cohort). Genotype-based tests of population differentiation using 23 SNPs across CARD15, together with estimates of FST, indicated that the German and Norwegian background populations could be differentiated at the CARD15 locus. The Norwegian and German CD samples exhibited particularly strong differentiation at the three predisposing loci and those marking their background haplotype. There were significantly lower frequencies of the CARD15 SNPs and no significant association with CD in the Norwegian samples. Only a marginal association was observed for the subphenotypes ileitis and ileocolitis vs colitis (P=0.048). The population attributable risk percentage (PAR{\%}) for CARD15 variants in the Norwegian cohort is the lowest reported for a European population (1.88{\%}), except Iceland. Similarly, the DLG5 variant showed no association with CD or IBD, however, there was a negative correlation with stricture (P=0.035). The present results are consistent with an emerging pattern of a low frequency of the CARD15 variants in Northern countries where the prevalence of IBD is greatest.",
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AU - Medici, Valentina

AU - Mascheretti, Silvia

AU - Croucher, Peter J P

AU - Stoll, Monika

AU - Hampe, Jochen

AU - Grebe, Jochen

AU - Sturniolo, Giacomo C.

AU - Solberg, Camilla

AU - Jahnsen, Jorgen

AU - Moum, Bjorn

AU - Schreiber, Stefan

AU - Vatn, Morten H.

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N2 - The first gene associated with Crohn disease (CD) has been identified as CARD15 (16q12). Three variants, R702W, G908R and 1007fsinsC are strongly and independently associated with the disease. A second gene, conveying a smaller risk for inflammatory bowel disease (IBD), has been identified as DLG5 (10q23). We assess the frequency of the CARD15 SNPs and of the R30Q mutation in DLG5 and their contribution to the development of CD in a cohort of unrelated IBD patients (151 CD, 325 ulcerative colitis (UC)) and healthy controls (236) from South-east Norway (IBSEN cohort). Genotype-based tests of population differentiation using 23 SNPs across CARD15, together with estimates of FST, indicated that the German and Norwegian background populations could be differentiated at the CARD15 locus. The Norwegian and German CD samples exhibited particularly strong differentiation at the three predisposing loci and those marking their background haplotype. There were significantly lower frequencies of the CARD15 SNPs and no significant association with CD in the Norwegian samples. Only a marginal association was observed for the subphenotypes ileitis and ileocolitis vs colitis (P=0.048). The population attributable risk percentage (PAR%) for CARD15 variants in the Norwegian cohort is the lowest reported for a European population (1.88%), except Iceland. Similarly, the DLG5 variant showed no association with CD or IBD, however, there was a negative correlation with stricture (P=0.035). The present results are consistent with an emerging pattern of a low frequency of the CARD15 variants in Northern countries where the prevalence of IBD is greatest.

AB - The first gene associated with Crohn disease (CD) has been identified as CARD15 (16q12). Three variants, R702W, G908R and 1007fsinsC are strongly and independently associated with the disease. A second gene, conveying a smaller risk for inflammatory bowel disease (IBD), has been identified as DLG5 (10q23). We assess the frequency of the CARD15 SNPs and of the R30Q mutation in DLG5 and their contribution to the development of CD in a cohort of unrelated IBD patients (151 CD, 325 ulcerative colitis (UC)) and healthy controls (236) from South-east Norway (IBSEN cohort). Genotype-based tests of population differentiation using 23 SNPs across CARD15, together with estimates of FST, indicated that the German and Norwegian background populations could be differentiated at the CARD15 locus. The Norwegian and German CD samples exhibited particularly strong differentiation at the three predisposing loci and those marking their background haplotype. There were significantly lower frequencies of the CARD15 SNPs and no significant association with CD in the Norwegian samples. Only a marginal association was observed for the subphenotypes ileitis and ileocolitis vs colitis (P=0.048). The population attributable risk percentage (PAR%) for CARD15 variants in the Norwegian cohort is the lowest reported for a European population (1.88%), except Iceland. Similarly, the DLG5 variant showed no association with CD or IBD, however, there was a negative correlation with stricture (P=0.035). The present results are consistent with an emerging pattern of a low frequency of the CARD15 variants in Northern countries where the prevalence of IBD is greatest.

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