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

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 delin...

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Published in:American journal of medical genetics 2003-09, Vol.121A (3), p.240-244
Main Authors: Fidder, Herma H., Olschwang, Sylviane, Avidan, Benjamin, Zouali, Habib, Lang, Alon, Bardan, Eytan, Picard, Orit, Bar-Meir, Simon, Colombel, Jean Frederic, Chowers, Yehuda
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creator Fidder, Herma H.
Olschwang, Sylviane
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Colombel, Jean Frederic
Chowers, Yehuda
description 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. © 2003 Wiley‐Liss, Inc.
doi_str_mv 10.1002/ajmg.a.20209
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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. 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J. Med. Genet</addtitle><description>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). 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J. Med. Genet</addtitle><date>2003-09-01</date><risdate>2003</risdate><volume>121A</volume><issue>3</issue><spage>240</spage><epage>244</epage><pages>240-244</pages><issn>1552-4825</issn><issn>0148-7299</issn><eissn>1552-4833</eissn><eissn>1096-8628</eissn><coden>AJMGDA</coden><abstract>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. © 2003 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>12923865</pmid><doi>10.1002/ajmg.a.20209</doi><tpages>5</tpages></addata></record>
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subjects Adult
Age of Onset
Alleles
Biological and medical sciences
CARD15
Carrier Proteins - genetics
Colitis, Ulcerative - genetics
Crohn Disease - ethnology
Crohn Disease - genetics
Crohn's disease
Female
Frameshift Mutation - genetics
Gastroenterology. Liver. Pancreas. Abdomen
Gene Frequency
genetic predisposition
Genetic Predisposition to Disease - genetics
Genotype
Germ-Line Mutation - genetics
Humans
Intracellular Signaling Peptides and Proteins
Israel - ethnology
Jewish
Jews - genetics
Male
Medical sciences
Mutation, Missense - genetics
NOD2
Nod2 Signaling Adaptor Protein
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
ulcerative colitis
title Association between mutations in the CARD15 (NOD2) gene and Crohn's disease in Israeli Jewish patients
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