Title: The TNF/ADAM 17 system: implication of an ADAM 17 haplotype in the clinical response to infliximab in Crohn's disease
Authors: Dideberg, Vinciane ×
Théâtre, Emilie
Farnir, Frédéric
Vermeire, Severine
Rutgeerts, Paul
Vos, Martine
Belaiche, Jacques
Franchimont, Denis
Gossum, André
Louis, Edouard
Bours, Vincent #
Issue Date: Oct-2006
Publisher: Lippincott Williams & Wilkins
Series Title: Pharmacogenetics and genomics vol:16 issue:10 pages:727-734
Abstract: Infliximab, a chimeric anti-tumour necrosis factor (TNF)-alpha antibody induces a clinical response in 70% of Crohn's disease patients and the response to infliximab therapy could be partially determined by genetic factors. The implication of both transmembrane and soluble forms of the TNF-alpha in the mechanism of action of infliximab has been demonstrated. The aim of our work was first to perform a complete study of TNF variants role in the response to infliximab in Crohn's disease. Secondly, considering the role of ADAM 17 in TNF-alpha shedding, the ADAM 17 locus was also studied. The response to infliximab was evaluated in 222 Caucasian Crohn's disease patients with a luminal (n=160) or fistulizing (n=62) form of the disease. Clinical and biological response evaluation was based on the Crohn's Disease Activity Index score and C-reactive protein level evolutions, respectively. The entire TNF gene was sequenced on the complete cohort. Twelve single nucleotide polymorphisms spanning the ADAM 17 locus were studied and haplotypes rebuilt. A clinical response was observed in 64% of the patients and biological response in 77.1% of patients. No association was found between the TNF gene and the response to infliximab. One haplotype in the ADAM 17 region was associated with a clinical response to infliximab in CD patients (adjusted P=0.045). In conclusion, our results exclude, with a reasonable power, an implication of the TNF gene in the response to infliximab in Crohn's disease, but reveal a potential role of the ADAM 17 gene in this response.
ISSN: 1744-6872
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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