Z Gastroenterol 2004; 42 - 78
DOI: 10.1055/s-2004-826979

Common NOD2/CARD15 alleles and other EXON4 mutations in 527 hungarian patients with Crohn's disease: Genotype-phenotype associations

L Lakatos 1, PL Lakatos 2, F Szalay 2, C Willheim-Polli 3, Z Tulassay 4, T Molnar 5, W Reinisch 3, C Österreicher 3, J Papp 2
  • 1Csolnoky County Hospital, Veszprem
  • 21st Dept. of Med, Semmelweis University, Budapest
  • 3Dept. of Intern. Med. 4, University of Vienna, Austria
  • 42nd Dept. of Med., Semmelweis University, Budapest
  • 51st Dept. of Med., University, Szeged

Background: Mutations of NOD2/CARD15 gene were identified as genetic markers in Crohn's disease (CD). Our aim was to determine the presence of common NOD2 mutation in 3 cohorts of Hungarian CD patients.

Patients and methods: 527 patients with CD (m/f: 265/262, age: 37.1 (SD 7.6)yrs) and 200 healthy subjects were investigated. DNA was screened for possible mutations by denaturing HPLC (WAVE-systems, UK) using published primers for SNP's 8,12, and 13. Mutations were confirmed by direct sequencing on ABI-Prism310 (Perkin Elmer, USA).

Results: NOD2/CARD15 mutations were found in 185 (35.1%) patients. SNP8 (10.8% vs. controls: 6%, p=0.02), SNP13 (19.4% vs. 5%, p<0.0001) and exon4 R703C (2.1% vs. controls: 0%, OR=6.89; 95%CI=1.18-((infin)), p=0.02) mutations were more frequent in CD. Carriage of one or two variant NOD2 allele was associated with increased risk for CD (ORhet=1.71; 95%CI=1.12–2.6, p=0.0001, ORhom=14.43; 95%CI=2.47-((infin)), p=0.0003, ORcomp=12.92; 95%CI=2.2-((infin)), p=0.0006). The presence of variant alleles was associated with ileal disease (81.9% vs. 69.5%, p=0.0029), stricturing behavior (21.1% vs. 31.1%, p=0.026) and younger disease onset (26.4 vs. 29.8yrs, p=0.0006), but not with duration, extraintestinal manifestations, familial disease, smoking habits or need for surgery.

Conclusions: In concordance with previous data R702W, 3020insC mutations are common in Hungarian patients with CD. We identified the carriage of R703C allele as a risk factor for CD. The presence of variant alleles was associated with younger disease onset, ileal disease and stricturing behavior.