TITLE

Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis

AUTHOR(S)
Franchimont, D.; Vermeke, S.; Housni, H.El; Pierik, M.; Van Steen, K.; Gustot, T.; Quertinmont, E.; Abramowicz, M.; Van Gossum, A.; Devière, J.; Rutgeerts, P.
PUB. DATE
July 2004
SOURCE
Gut;Jul2004, Vol. 53 Issue 7, p987
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and aims: Elicitation of an innate immune response to bacterial products is mediated through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs) and the NODs. The recently characterised Asp299Gly polymorphism in the lipopolysaccharide (LPS) receptor TLR4 is associated with impaired LPS signalling and increased susceptibility to Gram negative infections. We sought to determine whether this polymorphism was associated with Crohn's disease (CD) and/or ulcerative colitis (UC). Methods: Allele frequencies of the TLR4 Asp299Gly polymorphism and the three NOD2/CARD15 polymorphisms (Arg702Trp, Gly908Arg, and Leu1007fsinsC) were assessed in two independent cohorts of CD patients (cohort 1, n = 334; cohort 2, n = 114), in 163 UC patients, and in 140 controls. A transmission disequilibrium test (TDT) was then performed on 318 inflammatory bowel disease (IBD) trios. Results: The allele frequency of the TLR4 Asp299Gly polymorphism was significantly higher in CD (cohort 1: 11% v 5%, odds ratio (OR) 2.31 (95% confidence interval (Cl) 1.28-4.17), p = 0.004; and cohort 2: 12% v 5%, OR 2.45 (95% Cl 1.24-4.81), p = 0.007) and UC patients (10% v 5%, OR 2.05 (95% CI 1.07- 3.93), p = 0.027) compared with the control population. A TDT on 318 IBD trios demonstrated preferential transmission of the TLR4 Asp299Gly polymorphism from heterozygous parents to affected children (T/U: 68/34, p =0.01). Carrying polymorphisms in both TLR4 and NOD2 was associated with a genotype relative risk (RR) of 4.7 compared with a RR of 2.6 and 2.5 for TLR4 and NOD2 variants separately. Conclusion: We have reported on a novel association of the ILR4 Asp299Gly polymorphism with both CD and UC. This finding further supports the genetic influence of PRRs in triggering IBD.
ACCESSION #
13870130

 

Related Articles

  • Metronidazole and Ciprofloxacin for Pouchitis Treatment. Deresinski, Stan; Kwok-Yung Yuen // Clinical Infectious Diseases;3/15/2005, Vol. 40 Issue 6, p1 

    The article presents information on the use of metronidazole and ciprofloxacin for pouchitis treatment. Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Metronidazole and ciprofloxacin are commonly used for treatment; however, nothing is...

  • New IBD genetics: common pathways with other diseases. Lees, C. W.; Barrett, J. C.; Parkes, M.; Satsangi, J. // Gut;Dec2011, Vol. 60 Issue 12, p1739 

    Complex disease genetics has been revolutionised in recent years by the advent of genome-wide association (GWA) studies. The chronic inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis have seen notable successes culminating in the discovery of 99 published susceptibility...

  • Scientists explore pathogenesis of IBD. Hampton, Tracy // JAMA: Journal of the American Medical Association;12/8/2004, Vol. 292 Issue 22, p2708 

    Focuses on studies of inflammatory bowel disease (IBD). Question why some patients with IBD develop Crohn disease or ulcerative colitis; Factors that are believed to be necessary for IBD to develop; Description of the pathogenesis of IBD; Potential treatment for the management of the disease;...

  • Recent Indications and Methods of Surgery for Inflammatory Bowel Disease. S. Ohki; S. Terashima; K. Sekikawa; S. Takenoshita; M. Gotoh // Current Drug Targets - Inflammation & Allergy;Jun2003, Vol. 2 Issue 2, p113 

    Inflammatory bowel disease, notably ulcerative colitis (UC) or Crohn disease (CD), is basically benign, but sometimes develops into serious or fatal cancer. While the primary therapies are medical, such as pharmacotherapy and dietetic modification, intractable, serious, and cancerous cases can...

  • Ulcerative colitis. Ghosh, Subrata // BMJ: British Medical Journal (International Edition);04/22/2000, Vol. 320 Issue 7242, p1119 

    Provides information on ulcerative colitis. Clinical features and diagnosis; Etiology; Clinical management; Failure of medical management and its indications for surgery.

  • What's new in inflammatory bowel disease in 2008? Baumgart, Daniel C. // World Journal of Gastroenterology;1/21/2008, Vol. 14 Issue 3, p329 

    Ulcerative colitis and Crohn's disease represent the two major forms of inflammatory bowel disease. In this highlight topic series of articles we cover the latest developments in genetics and epidemiology, intestinal physiology, mucosal immunology, mechanisms of epithelial cell injury and...

  • PREVALENCE AND MANAGEMENT OF INFLAMMATORY BOWEL DISEASE: DATA FROM PRIMARY CARE RECORDS, INCLUDING 5-ASA PRESCRIBING AND COMPLIANCE. Stone, M.A.; Mayberry, J.F.; Baker, R.B. // Gut;Apr2003 Supplement 1, Vol. 52, pA68 

    Background: Data from general practice (GP) records in North Tees (Rubin et al, 2000) suggested a higher prevalence of inflammatory bowel disease (IBD) than previous estimates from hospital data. Regular prescribing of 5-aminosalicylic acid (5-ASA) therapy can reduce the risk of colorectal...

  • Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease. Attinkara, Ragam; Mwinyi, Jessica; Truninger, Kaspar; Regula, Jaroslaw; Gaj, Pawel; Rogler, Gerhard; Kullak-Ublick, Gerd A.; Eloranta, Jyrki J. // BMC Research Notes;2012, Vol. 5 Issue 1, p461 

    Background: Pathogenesis of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), involves interaction between environmental factors and inappropriate immune responses in the intestine of genetically predisposed individuals. Bile acids and their nuclear receptor,...

  • ASSOCIATION OF MULTIDRUG RESISTANCE GENE (MDRJ) C3435T POLYMORPHISM WITH EXTENSIVE AND SEVERE ULCERATIVE COLITIS (UC). Ho, G. T.; Nimmo, E.; Fennell, J.; Drummond, H.; Goddard, C.; Mowat, C.; Satsangi, J. // Gut;Apr2004 Supplement 3, Vol. 53, pA4 

    The multidrug resistance gene (MDR1) gene encodes a transmembrane efflux pump which is highly expressed on intestinal epithelial cells. The ulcerative colitis (UC) like phenotype in mdrla-deficient mice and the position of the gene within chromosome 7q22, together with recent genetic studies...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics