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Haplotype of prostaglandin synthase 2/cyclooxygenase 2 is involved in the susceptibility to inflammatory bowel disease

Haplotype of prostaglandin synthase 2/cyclooxygenase 2 is involved in the susceptibility to inflammatory bowel disease

作     者:David G Cox J Bart A Crusius Petra HM Peeters H Bas Bueno-de-Mesquita A Salvador Pe(n|~)a Federico Canzian 

作者机构:International Agency for Research on Cancer Laboratory of Immunogenetics Julius Center for Health Sciences and Primary Care Department of Epidemiology Laboratory of Immunogenetics and Department of Gastroenterology 

出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))

年 卷 期:2005年第11卷第38期

页      面:6003-6008页

核心收录:

学科分类:1002[医学-临床医学] 100201[医学-内科学(含:心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基  金: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)the Crohn's and Colitis Foundation of America (to ASP) 

主  题:Inflammatory bowel disease Prostaglandin G/H synthase Cyclooxygenase SNP Haplotype 

摘      要: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 PTG52 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 ulcerativecolitis (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.

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