Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations

Peter Laszlo Lakatos, Laszlo Lakatos, Ferenc Szalay, Claudia Willheim-Polli, Christoph Österreicher, Zsolt Tulassay, Tamas Molnar, Walter Reinisch, Janos Papp, Gyula Mozsik, Peter Ferenci, Peter Fuszek, Peter Vargha, Laszlo Pronai, Annamaria Nemeth, Pal Miheller, Agota Kovacs, Laszlo Bene, Gyorgy Szekely, Beata GasztonyiFerenc Nagy, Janos Lonovics, Laszlo Ujszaszy, Istvan Altorjai, Karoly Palatka, Gyula G. Kiss, Ferenc Tarnok, Zoltan Dobronte, Zsuzsanna Erdelyi, Tunde Pandur, Gabor Mester

Research output: Article

116 Citations (Scopus)


Aim: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. Methods: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. Results: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%, P<0.0001). SNP8/R702W (10.8% vs 6%, P = 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P = 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet = 1.71, 95%CI = 1.12-2.6, P = 0.0001, ORtwo-risk alleles = 25.2, 95%CI = 4.37- , P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P = 0.0006), ileal disease (81.9% vs 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P = 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69, 95%CI = 1.13-2.55, P = 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P = 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. Conclusion: These results confirm that variant NOD2/CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.

Original languageEnglish
Pages (from-to)1489-1495
Number of pages7
JournalWorld journal of gastroenterology
Issue number10
Publication statusPublished - márc. 14 2005

ASJC Scopus subject areas

  • Gastroenterology

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