DLC5 R30Q is not associated with IBD in Hungarian IBD patients but predicts clinical response to steroids in Crohn's disease

P. Lakatos, S. Fischer, Karolien Claes, A. Kovács, T. Molnár, I. Altorjay, P. Demeter, Z. Tulassay, K. Palatka, M. Papp, Paul Rutgeerts, F. Szalay, J. Papp, Severine Vermeire, L. Lakatos, P. Fuszek, P. Vargha, Janos OsztovicsJ., L. Bene, F. NagyJ. Lonovics, Levente Balint, Ferenc Huoranszky, Istvan Dobo, L. Herszényi, P. Miheller, A. Németh, Z. Erdélyi, G. Mester, Csaba Molnar, T. Pandúr

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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% CI 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% CI 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.

Original languageEnglish
Pages (from-to)362-368
Number of pages7
JournalInflammatory Bowel Diseases
Volume12
Issue number5
DOIs
Publication statusPublished - May 2006

Fingerprint

Inflammatory Bowel Diseases
Crohn Disease
Steroids
Alleles
Ulcerative Colitis
Germany
Healthy Volunteers
Logistic Models
Odds Ratio
Disease Susceptibility
Genetic Association Studies
Genetic Markers
Restriction Fragment Length Polymorphisms
High Pressure Liquid Chromatography
Phenotype
Recurrence
Polymerase Chain Reaction
Mutation
DNA
Population

Keywords

  • DLG5
  • IBD
  • Infliximab
  • NOD2
  • Phenotype
  • Steroid resistance
  • TLR4

ASJC Scopus subject areas

  • Gastroenterology

Cite this

@article{478aed952af349ffbe5c295f1717a662,
title = "DLC5 R30Q is not associated with IBD in Hungarian IBD patients but predicts clinical response to steroids in Crohn's disease",
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{\%} CI 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{\%} CI 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.",
keywords = "DLG5, IBD, Infliximab, NOD2, Phenotype, Steroid resistance, TLR4",
author = "P. Lakatos and S. Fischer and Karolien Claes and A. Kov{\'a}cs and T. Moln{\'a}r and I. Altorjay and P. Demeter and Z. Tulassay and K. Palatka and M. Papp and Paul Rutgeerts and F. Szalay and J. Papp and Severine Vermeire and L. Lakatos and P. Fuszek and P. Vargha and Janos OsztovicsJ. and L. Bene and F. Nagy and J. Lonovics and Levente Balint and Ferenc Huoranszky and Istvan Dobo and L. Hersz{\'e}nyi and P. Miheller and A. N{\'e}meth and Z. Erd{\'e}lyi and G. Mester and Csaba Molnar and T. Pand{\'u}r",
year = "2006",
month = "5",
doi = "10.1097/01.MIB.0000217336.38312.09",
language = "English",
volume = "12",
pages = "362--368",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - DLC5 R30Q is not associated with IBD in Hungarian IBD patients but predicts clinical response to steroids in Crohn's disease

AU - Lakatos, P.

AU - Fischer, S.

AU - Claes, Karolien

AU - Kovács, A.

AU - Molnár, T.

AU - Altorjay, I.

AU - Demeter, P.

AU - Tulassay, Z.

AU - Palatka, K.

AU - Papp, M.

AU - Rutgeerts, Paul

AU - Szalay, F.

AU - Papp, J.

AU - Vermeire, Severine

AU - Lakatos, L.

AU - Fuszek, P.

AU - Vargha, P.

AU - OsztovicsJ., Janos

AU - Bene, L.

AU - Nagy, F.

AU - Lonovics, J.

AU - Balint, Levente

AU - Huoranszky, Ferenc

AU - Dobo, Istvan

AU - Herszényi, L.

AU - Miheller, P.

AU - Németh, A.

AU - Erdélyi, Z.

AU - Mester, G.

AU - Molnar, Csaba

AU - Pandúr, T.

PY - 2006/5

Y1 - 2006/5

N2 - 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% CI 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% CI 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.

AB - 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% CI 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% CI 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.

KW - DLG5

KW - IBD

KW - Infliximab

KW - NOD2

KW - Phenotype

KW - Steroid resistance

KW - TLR4

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UR - http://www.scopus.com/inward/citedby.url?scp=33646759253&partnerID=8YFLogxK

U2 - 10.1097/01.MIB.0000217336.38312.09

DO - 10.1097/01.MIB.0000217336.38312.09

M3 - Article

C2 - 16670524

AN - SCOPUS:33646759253

VL - 12

SP - 362

EP - 368

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 5

ER -