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

Type = Article
Cím:
Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations
Létrehozó:
Lakatos, Péter László
Lakatos, László
Szalay, Ferenc
Willheim-Polli, Claudia
Oesterreicher, Christoph
Tulassay, Zsolt
Molnár, Tamás
Reinisch, Walter
Papp, János
Mózsik, Gyula
Ferenci, Péter
Kiadó:
Beijing Baishideng BioMed Scientific Co.
Dátum:
2005
Téma:
RC Internal medicine / belgyógyászat
Tartalmi leírás:
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 (OR(het) = 1.71, 95% CI = 1.12-2.6, P = 0.0001, OR(two-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, extraintestinal 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. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.
Típus:
Article
NonPeerReviewed
Formátum:
application/pdf
Azonosító:
Lakatos, Péter László and Lakatos, László and Szalay, Ferenc and Willheim-Polli, Claudia and Oesterreicher, Christoph and Tulassay, Zsolt and Molnár, Tamás and Reinisch, Walter and Papp, János and Mózsik, Gyula and Ferenci, Péter (2005) Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations. World Journal of Gastroenterology, 11 (10). pp. 1489-1495. ISSN 1007-9327 (print), 2219-2840 (online)
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