Clinical Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2005; 11(5): 681-685
Published online Feb 7, 2005. doi: 10.3748/wjg.v11.i5.681
Association between polymorphisms in the Toll-like receptor 4, CD14, and CARD15/NOD2 and inflammatory bowel disease in the Greek population
Maria Gazouli, Gerassimos Mantzaris, Athanassios Kotsinas, Panayotis Zacharatos, Efstathios Papalambros, Athanassios Archimandritis, John Ikonomopoulos, Vassilis G Gorgoulis
Maria Gazouli, Athanassios Kotsinas, Panayotis Zacharatos, Vassilis G Gorgoulis, Department of Histology-Embryology, School of Medicine, University of Athens, 11527 Athens, Greece
Gerassimos Mantzaris, Department of Gastroenterology, “Evagelismos” Hospital, 11521 Athens, Greece
Efstathios Papalambros, First Department of Surgery, Laikon Hospital, School of Medicine, University of Athens, 11527 Athens, Greece
Athanassios Archimandritis, Department of Pathophysiology, Gastroenterology Section, School of Medicine, University of Athens, “Hippocration” Hospital, 11527 Athens, Greece
John Ikonomopoulos, Agricultural University of Athens, Department of Anatomy-Physiology, Faculty of Animal Science, 11855 Athens, Greece
Author contributions: All authors contributed equally to the work.
Supported by the EU Project “Sacrohn” N. QLK2-CT-2000-00928
Correspondence to: Dr. Vassilis G Gorgoulis, Department of Histology-Embryology, 53 Antaiou St. Ano Patisia, 11146 Athens, Greece. histoclub@ath.forthnet.gr
Fax: +302106535894
Received: May 25, 2004
Revised: May 28, 2004
Accepted: July 17, 2004
Published online: February 7, 2005
Abstract

AIM: Crohn’s disease (CD) and ulcerative colitis (UC) are multifactorial diseases with a significant genetic background. Apart from CARD15/NOD2 gene, evidence is accumulating that molecules related to the innate immune response such as CD14 or Toll-like receptor 4 (TLR4), are involved in their pathogenesis. In further exploring the genetic background of these diseases, we investigated the variations in the CARD15/NOD2 gene (Arg702Trp, Gly908Arg and Leu1007fsinsC), and polymorphisms in the TLR4 gene (Asp299Gly and Thr399Ile) as well as in the promoter of the CD14 gene (T/C at position -159) in Greek patients with CD and UC.

METHODS: DNA was obtained from 120 patients with CD, 85 with UC and 100 healthy individuals. Genotyping was performed by allele specific PCR or by PCR-RFLP analysis.

RESULTS: The 299Gly allele frequency of the TLR4 gene and the T allele and TT genotype frequencies of the CD14 promoter were significantly higher in CD patients only compared to healthy individuals (P = 0.026<0.05; P = 0.0048<0.01 and P = 0.047<0.05 respectively). Concerning the NOD2/CARD15 mutations the overall presence in CD patients was significantly higher than that in UC patients or in controls. Additionally, 51.67% of the CD patients were carriers of a TLR4 and/or CD14 polymorphic allele and at least one variant of the NOD2/CARD15, compared to 27% of the UC patients. It should be pointed out that both frequencies significantly increased as compared with the 10% frequency of multiple carriers found in healthy controls. A possible interaction of the NOD2/CARD15 with TLR4 and especially CD14, increased the risk of developing inflammatory bowel disease (IBD).

CONCLUSION: Our results indicate that co-existence of a mutation in either the TLR4 or CD14 gene, and in NOD2/CARD15 is associated with an increased susceptibility to developing CD compared to UC, and to developing either CD or UC compared to healthy individuals.

Keywords: Inflammatory bowel disease; CARD15/NOD2 gene; Toll-like receptor 4; CD14 Antigen