Brief Reports
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2005; 11(38): 6003-6008
Published online Oct 14, 2005. doi: 10.3748/wjg.v11.i38.6003
Haplotype of prostaglandin synthase 2/cyclooxygenase 2 is involved in the susceptibility to inflammatory bowel disease
David G Cox, J Bart A Crusius, Petra HM Peeters, H Bas Bueno-de-Mesquita, A Salvador Peña, Federico Canzian
David G Cox, International Agency for Research on Cancer, Lyon, France (Current address: Molecular Epidemiology, Harvard School of Public Health, Boston, MA, USA)
J Bart A Crusius, Laboratory of Immunogenetics, VU University Medical Center, Amsterdam, The Netherlands
Petra HM Peeters, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
H Bas Bueno-de-Mesquita, Department of Epidemiology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands
A Salvador Peña, Laboratory of Immunogenetics and Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands
Federico Canzian, International Agency for Research on Cancer, Lyon, France (Current address: German Cancer Research Center, Heidelberg, Germany)
Author contributions: All authors contributed equally to the work.
Supported by The Grants from the International Agency for Research on Cancer (Special Training Award to DGC), the French Association for Research on Cancer (grant #7478), and the Crohn's and Colitis Foundation of America (to ASP)
Correspondence to: Federico Canzian, PhD, German Cancer Research Centre (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. f. canzian@dkfz.de
Telephone: +49-6221-421791 Fax: +49-6221-421810
Received: January 21, 2005
Revised: February 15, 2005
Accepted: February 18, 2005
Published online: October 14, 2005
Abstract

AIM: Prostaglandin G/H synthase 2 (PTGS2 or COX2) is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases (IBD). In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD.

METHODS: We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTGS2 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5 exonuclease assay (TaqMan). New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing.

RESULTS: Allele 5209G was weakly associated with Crohn's disease (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57), and allele 8473T with ulcerative colitis (OR 1.50, 95%CI 1.00-2.27). The haplotype including both alleles showed a strong association with IBD (OR 13.15, 95%CI 3.17-116.15). This haplotype, while rare (-0.3%) in the general population, is found more frequently in patients (3.5%).

CONCLUSION: Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.

Keywords: Inflammatory bowel disease, Prostaglandin G/H synthase, Cyclooxygenase, SNP, Haplotype