[en] 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Dideberg, Vinciane ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
Theatre, Emilie ; Université de Liège - ULiège > Génétique générale et humaine
Farnir, Frédéric ; Université de Liège - ULiège > Département de productions animales > Biostatistique, économie, sélection animale
Vermeire, S.
Rutgeerts, P.
Vos, M. D.
Belaiche, Jacques ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Franchimont, D.
Gossum, A. V.
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine
Language :
English
Title :
The Tnf/Adam 17 System: Implication of an Adam 17 Haplotype in the Clinical Response to Infliximab in Crohn's Disease
Publication date :
October 2006
Journal title :
Pharmacogenetics and Genomics
ISSN :
1744-6872
eISSN :
1744-6880
Publisher :
Lippincott Williams & Wilkins, United States - Pennsylvania
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