Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease

Maria T Abreu, Kent D. Taylor, Ying Chao Lin, Tieu Hang, Joanne Gaiennie, Carol J. Landers, Eric A. Vasiliauskas, Lori Y. Kam, Micha Rojany, Konstantinos A. Papadakis, Jerome I. Rotter, Stephan R. Targan, Huiying Yang

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Abstract

Background & Aims: The clinical manifestations of Crohn's disease (CD) are diverse, ranging from fibrostenosing small-bowel disease to colon-predominant inflammation. These distinctions may represent genetic, immunologic, and microbial heterogeneity. NOD2 gene mutations in CD have been described recently and may alter innate immune responses. We hypothesized that NOD2 mutations may be associated with distinct phenotypic expressions of CD. Methods: Two cohorts of consecutively identified patients referred to an inflammatory bowel disease center (n = 142 collected between 1993 and 1996; n = 59 collected between 1999 and 2001) were genotyped for 3 single nucleotide variants of NOD2-R675W, G881R, and 3020insC-and phenotyped for disease behavior, disease location, and serum immune markers. Results: Univariate analysis showed that CD-associated NOD2 variants were significantly associated with fibrostenosing disease in each cohort (P = 0.049 and P = 0.002, respectively). When both cohorts were analyzed together, the association between NOD2 variants and fibrostenosing disease was more significant (P = 0.001). These relationships were observed in both Jews and non-Jews. Forty-six percent of patients with fibrostenosing disease carried at least I of these alleles, compared with only 23.5% of patients without fibrostenosing disease (odds ratio, 2.8; 95% confidence interval, 1.6-5.2). Multivariate and conditioning analyses showed a primary association between NOD2 allelic variants and fibrostenosing disease, but not with small-bowel disease. Conclusions: In this description of a genotype/phenotype correlation in CD patients and NOD2 variants, data suggest that variation in this gene contributes to the occurrence of fibrostenotic CD of the small bowel.

Original languageEnglish
Pages (from-to)679-688
Number of pages10
JournalGastroenterology
Volume123
Issue number3
DOIs
StatePublished - Sep 1 2002
Externally publishedYes

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Crohn Disease
Mutation
Microbial Genetics
Biomarkers
Jews
Genetic Association Studies
Inflammatory Bowel Diseases
Innate Immunity
Genes
Colon
Multivariate Analysis
Nucleotides
Alleles
Odds Ratio
Confidence Intervals
Inflammation

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Abreu, M. T., Taylor, K. D., Lin, Y. C., Hang, T., Gaiennie, J., Landers, C. J., ... Yang, H. (2002). Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease. Gastroenterology, 123(3), 679-688. https://doi.org/10.1053/gast.2002.35393

Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease. / Abreu, Maria T; Taylor, Kent D.; Lin, Ying Chao; Hang, Tieu; Gaiennie, Joanne; Landers, Carol J.; Vasiliauskas, Eric A.; Kam, Lori Y.; Rojany, Micha; Papadakis, Konstantinos A.; Rotter, Jerome I.; Targan, Stephan R.; Yang, Huiying.

In: Gastroenterology, Vol. 123, No. 3, 01.09.2002, p. 679-688.

Research output: Contribution to journalArticle

Abreu, MT, Taylor, KD, Lin, YC, Hang, T, Gaiennie, J, Landers, CJ, Vasiliauskas, EA, Kam, LY, Rojany, M, Papadakis, KA, Rotter, JI, Targan, SR & Yang, H 2002, 'Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease', Gastroenterology, vol. 123, no. 3, pp. 679-688. https://doi.org/10.1053/gast.2002.35393
Abreu, Maria T ; Taylor, Kent D. ; Lin, Ying Chao ; Hang, Tieu ; Gaiennie, Joanne ; Landers, Carol J. ; Vasiliauskas, Eric A. ; Kam, Lori Y. ; Rojany, Micha ; Papadakis, Konstantinos A. ; Rotter, Jerome I. ; Targan, Stephan R. ; Yang, Huiying. / Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease. In: Gastroenterology. 2002 ; Vol. 123, No. 3. pp. 679-688.
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abstract = "Background & Aims: The clinical manifestations of Crohn's disease (CD) are diverse, ranging from fibrostenosing small-bowel disease to colon-predominant inflammation. These distinctions may represent genetic, immunologic, and microbial heterogeneity. NOD2 gene mutations in CD have been described recently and may alter innate immune responses. We hypothesized that NOD2 mutations may be associated with distinct phenotypic expressions of CD. Methods: Two cohorts of consecutively identified patients referred to an inflammatory bowel disease center (n = 142 collected between 1993 and 1996; n = 59 collected between 1999 and 2001) were genotyped for 3 single nucleotide variants of NOD2-R675W, G881R, and 3020insC-and phenotyped for disease behavior, disease location, and serum immune markers. Results: Univariate analysis showed that CD-associated NOD2 variants were significantly associated with fibrostenosing disease in each cohort (P = 0.049 and P = 0.002, respectively). When both cohorts were analyzed together, the association between NOD2 variants and fibrostenosing disease was more significant (P = 0.001). These relationships were observed in both Jews and non-Jews. Forty-six percent of patients with fibrostenosing disease carried at least I of these alleles, compared with only 23.5{\%} of patients without fibrostenosing disease (odds ratio, 2.8; 95{\%} confidence interval, 1.6-5.2). Multivariate and conditioning analyses showed a primary association between NOD2 allelic variants and fibrostenosing disease, but not with small-bowel disease. Conclusions: In this description of a genotype/phenotype correlation in CD patients and NOD2 variants, data suggest that variation in this gene contributes to the occurrence of fibrostenotic CD of the small bowel.",
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T1 - Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease

AU - Abreu, Maria T

AU - Taylor, Kent D.

AU - Lin, Ying Chao

AU - Hang, Tieu

AU - Gaiennie, Joanne

AU - Landers, Carol J.

AU - Vasiliauskas, Eric A.

AU - Kam, Lori Y.

AU - Rojany, Micha

AU - Papadakis, Konstantinos A.

AU - Rotter, Jerome I.

AU - Targan, Stephan R.

AU - Yang, Huiying

PY - 2002/9/1

Y1 - 2002/9/1

N2 - Background & Aims: The clinical manifestations of Crohn's disease (CD) are diverse, ranging from fibrostenosing small-bowel disease to colon-predominant inflammation. These distinctions may represent genetic, immunologic, and microbial heterogeneity. NOD2 gene mutations in CD have been described recently and may alter innate immune responses. We hypothesized that NOD2 mutations may be associated with distinct phenotypic expressions of CD. Methods: Two cohorts of consecutively identified patients referred to an inflammatory bowel disease center (n = 142 collected between 1993 and 1996; n = 59 collected between 1999 and 2001) were genotyped for 3 single nucleotide variants of NOD2-R675W, G881R, and 3020insC-and phenotyped for disease behavior, disease location, and serum immune markers. Results: Univariate analysis showed that CD-associated NOD2 variants were significantly associated with fibrostenosing disease in each cohort (P = 0.049 and P = 0.002, respectively). When both cohorts were analyzed together, the association between NOD2 variants and fibrostenosing disease was more significant (P = 0.001). These relationships were observed in both Jews and non-Jews. Forty-six percent of patients with fibrostenosing disease carried at least I of these alleles, compared with only 23.5% of patients without fibrostenosing disease (odds ratio, 2.8; 95% confidence interval, 1.6-5.2). Multivariate and conditioning analyses showed a primary association between NOD2 allelic variants and fibrostenosing disease, but not with small-bowel disease. Conclusions: In this description of a genotype/phenotype correlation in CD patients and NOD2 variants, data suggest that variation in this gene contributes to the occurrence of fibrostenotic CD of the small bowel.

AB - Background & Aims: The clinical manifestations of Crohn's disease (CD) are diverse, ranging from fibrostenosing small-bowel disease to colon-predominant inflammation. These distinctions may represent genetic, immunologic, and microbial heterogeneity. NOD2 gene mutations in CD have been described recently and may alter innate immune responses. We hypothesized that NOD2 mutations may be associated with distinct phenotypic expressions of CD. Methods: Two cohorts of consecutively identified patients referred to an inflammatory bowel disease center (n = 142 collected between 1993 and 1996; n = 59 collected between 1999 and 2001) were genotyped for 3 single nucleotide variants of NOD2-R675W, G881R, and 3020insC-and phenotyped for disease behavior, disease location, and serum immune markers. Results: Univariate analysis showed that CD-associated NOD2 variants were significantly associated with fibrostenosing disease in each cohort (P = 0.049 and P = 0.002, respectively). When both cohorts were analyzed together, the association between NOD2 variants and fibrostenosing disease was more significant (P = 0.001). These relationships were observed in both Jews and non-Jews. Forty-six percent of patients with fibrostenosing disease carried at least I of these alleles, compared with only 23.5% of patients without fibrostenosing disease (odds ratio, 2.8; 95% confidence interval, 1.6-5.2). Multivariate and conditioning analyses showed a primary association between NOD2 allelic variants and fibrostenosing disease, but not with small-bowel disease. Conclusions: In this description of a genotype/phenotype correlation in CD patients and NOD2 variants, data suggest that variation in this gene contributes to the occurrence of fibrostenotic CD of the small bowel.

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