Variation at NOD2/CARD15 in Familial and Sporadic Cases of Crohn's Disease in the Ashkenazi Jewish Population

Zhou, Zhifeng; Lin, Xingyu; Akolkar, Pradip N.; Gulwani‐Akolkar, Beena; Levine, Jeremiah; Katz, Seymour; Silver, Jack

doi:10.1111/j.1572-0241.2002.07105.x

Cited by 53 publications

(21 citation statements)

References 17 publications

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“…Our results are in line with the observations by Akolkar et al [2001], who observed strong linkage to the IBD1 locus in Ashkenazi Jewish CD patients with early onset disease, and recently reported a lower age-of-onset in familial cases of CD in Ashkenazi Jewish CARD15 mutation carriers [Zhou et al, 2002]. Two European studies also reported a younger age of presentation in CARD15 carriers [Ahmad et al, 2002;Lesage et al, 2002].…”

Section: Discussionsupporting

confidence: 95%

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

Fidder

Olschwang

Avidan

et al. 2003

American J of Med Genetics Pt A

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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.

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Section: Discussionsupporting

confidence: 95%

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

Fidder

Olschwang

Avidan

et al. 2003

American J of Med Genetics Pt A

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“…Many individual studies have found an association between early-onset Crohn disease and NOD2 genetic variants (5, 12, 16 -21 ), indirectly suggesting that NOD2 genetic variants could be more frequent in children with Crohn disease than in adults with the disease; however, our metaanalysis provided no support for this hypothesis. Five case-control studies directly compared allele frequencies and risk estimates of NOD2 genetic variants for familial and sporadic cases of Crohn disease (16,20,22,24 ). Three of these studies found no significant difference (16,20,23 ), and the other 2 studies obtained higher risk estimates among familial cases than among sporadic cases (22,24 ).…”

Section: Discussionmentioning

confidence: 99%

“…Five case-control studies directly compared allele frequencies and risk estimates of NOD2 genetic variants for familial and sporadic cases of Crohn disease (16,20,22,24 ). Three of these studies found no significant difference (16,20,23 ), and the other 2 studies obtained higher risk estimates among familial cases than among sporadic cases (22,24 ). Nevertheless, our findings in the present metaanalysis indicating similarly increased odds ratios for Crohn disease for the NOD2 genetic variants in both familial and sporadic cases suggest that NOD2 genetic variants are not involved in the predisposition to familial clustering of Crohn disease.…”

Section: Discussionmentioning

confidence: 99%

Genotyping for NOD2 Genetic Variants and Crohn Disease: a Metaanalysis

2009

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Background: Arg702Trp, Gly908Arg, and Leu1007fsinsC variants of the NOD2 gene (nucleotide-binding oligomerization domain containing 2; alias, CARD15) influence the risk of Crohn disease. Methods: We conducted a systematic review to examine whether Arg702Trp, Gly908Arg, and Leu1007fsinsC are equally important risk factors for Crohn disease. In addition, we used studies for which combined information from all genotypes was available to compare risks in simple heterozygotes, compound heterozygotes, and homozygotes. PubMed, EMBASE, and Web of Science were searched. Seventy-five articles (18 727 cases and 17 102 controls) met the inclusion criteria and contributed data to the metaanalyses. Results: The odds ratios per allele for Crohn disease were 2.2 (95% CI, 2.0–2.5) for Arg702Trp, 2.6 (2.2–2.9) for Gly908Arg, and 3.8 (3.4–4.3) for Leu1007fsinsC (z-test results: Arg702Trp vs Gly908Arg, P = 0.03; Arg702Trp vs Leu1007fsinsC, P < 0.001; Gly908Arg vs Leu1007fsinsC, P < 0.001). When all 3 genotypes were combined, odds ratios for Crohn disease were 2.4 (95% CI, 2.0–2.8) for simple heterozygotes, 9.0 (6.0–13.5) for compound heterozygotes, and 6.7 (4.1–10.9) for homozygotes, compared with noncarriers (z-test results: simple heterozygotes vs compound heterozygotes, P < 0.001; simple heterozygotes vs homozygotes, P < 0.001; compound heterozygotes vs homozygotes, P = 0.18). Conclusions: The per-allele risk of Crohn disease was markedly higher for Leu1007fsinsC than for Arg702Trp and Gly908Arg. Combining all genotypes revealed the risks of Crohn disease for compound heterozygotes and homozygotes to be similar and markedly higher than for simple heterozygotes.

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“…The Irish CD group comprised 113 patients (77 females and 36 males) with a median age at diagnosis of 27.5 years (IQR [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. This corresponded to 38 patients diagnosed before the age of 40 years (A1) and 21 diagnosed after the age of 40 years (A2).…”

Section: Irish Patient Cohortmentioning

confidence: 99%

NOD2/CARD15, TLR4 and CD14 mutations in Scottish and Irish Crohn's disease patients: evidence for genetic heterogeneity within Europe?

et al. 2004

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Variation at NOD2/CARD15 in Familial and Sporadic Cases of Crohn's Disease in the Ashkenazi Jewish Population

Cited by 53 publications

References 17 publications

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

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

Genotyping for NOD2 Genetic Variants and Crohn Disease: a Metaanalysis

NOD2/CARD15, TLR4 and CD14 mutations in Scottish and Irish Crohn's disease patients: evidence for genetic heterogeneity within Europe?

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