TY - JOUR
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
N1 - Funding Information:
Supported by grants DK 46763 and DK 54967, the Cedars–Sinai Board of Governors' Chair in Medical Genetics, and the Feintech Family Chair in Inflammatory Bowel Disease.
PY - 2002/9
Y1 - 2002/9
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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U2 - 10.1053/gast.2002.35393
DO - 10.1053/gast.2002.35393
M3 - Article
C2 - 12198692
AN - SCOPUS:0036725827
SN - 0016-5085
VL - 123
SP - 679
EP - 688
JO - Gastroenterology
JF - Gastroenterology
IS - 3
ER -