Reference : The Tnf/Adam 17 System: Implication of an Adam 17 Haplotype in the Clinical Response ...
Scientific journals : Article
Life sciences : Genetics & genetic processes
http://hdl.handle.net/2268/34979
The Tnf/Adam 17 System: Implication of an Adam 17 Haplotype in the Clinical Response to Infliximab in Crohn's Disease
English
Dideberg, Vinciane mailto [Centre Hospitalier Universitaire de Liège - CHU > > Génétique >]
Theatre, Emilie [Université de Liège - ULg > > Génétique générale et humaine >]
Farnir, Frédéric mailto [Université de Liège - ULg > Département de productions animales > Biostatistique, économie, sélection animale >]
Vermeire, S. [> > > >]
Rutgeerts, P. [> > > >]
Vos, M. D. [> > > >]
Belaiche, Jacques mailto [Université de Liège - ULg > Département des sciences cliniques > Hépato-gastroentérologie]
Franchimont, D. [> > > >]
Gossum, A. V. [> > > >]
Louis, Edouard mailto [Université de Liège - ULg > Département des sciences cliniques > Hépato-gastroentérologie >]
Bours, Vincent mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Génétique générale et humaine]
Oct-2006
Pharmacogenetics and Genomics
16
10
727-734
Yes (verified by ORBi)
International
1744-6872
[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.
http://hdl.handle.net/2268/34979
10.1097/01.fpc.0000230117.26581.a4

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