DLG5 R30Q Is Not Associated With IBD in Hungarian IBD Patients but Predicts Clinical Response to Steroids in Crohn's Disease

Lakatos, Péter László and Fischer, Simon and Claes, Karolien and Kovács, Ágota and Molnár, Tamás and Altorjay, István and Demeter, Pál and Tulassay, Zsolt and Palatka, Károly and Papp, Mária and Rutgeerts, Paul and Szalay, Ferenc and Papp, János and Vermeire, Severine and Lakatos, László (2006) DLG5 R30Q Is Not Associated With IBD in Hungarian IBD Patients but Predicts Clinical Response to Steroids in Crohn's Disease. Inflammatory Bowel Diseases, 12 (5). pp. 362-368. ISSN 1078-0998 (print), 1536-4844 (online)

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Abstract

Background: Recent data Suggest that haplotypic variants of the DLG5 gene on 10q23 are associated with Susceptibility to inflammatory bowel disease (IBD) in Germany. In view of the geographical differences in frequency of genetic markers and the absence of data in Central European patients, our aim was to determine the DLG5 R30Q variant in Hungarian IBD patients. Materials and Methods: We investigated 773 unrelated IBD patients (age 38.1 +/- 10.3 years; duration, 8.8 +/- 7.5 years; Crohn's disease [CD]: 639; male/female, 309/330; duration, 8.4 +/- 7.1 years; ulcerative colitis [UC]: 134; male/female, 63/71; duration, 10.6 +/- 8.9 years) and 150 healthy subjects. DLG5 R30Q and TLR4 D299G variants were tested by polymerase chain reaction/restriction fragment length polymorphism. DNA was screened for NOD2/ CARD15 Mutations by denaturing high-performance liquid chromatography. Detailed clinical phenotype was determined by reviewing the medical charts. Results: The carrier frequency of the R30Q variant allele was not significantly different in IBD (22.0%), CD (20.8%), and UC (27.6%) patients compared with healthy control subjects (28.0%). In CD, the 113A variant allele was associated with steroid resistance (16.3% vs noncarriers, 7.6%; odds ratio [OR], 2.4; 95% Cl 1.3-4.5; P = 0.013). In a logistic regression model carriage of DLG5 R30Q, perianal involvement and frequent relapses were independently associated with steroid resistance. No phenotype-genotype associations were found in UC patients, although a trend toward more extensive disease was observed in carriers of the variant allele (OR 2.1; 95% Cl 0.95-4.4; P = 0.07). Conclusions: The present data strongly contrast previous data from Germany. DLG5 113A is not associated with disease susceptibility, but there was a tendency for this allele to confer resistance to steroids. Further studies are required to evaluate the significance of DLG5 in other populations from geographically diverse regions.

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