The TNF/ADAM 17 system: implication of an ADAM 17 haplotype in the clinical response to infliximab in Crohn's disease.
Pharmacogenet Genomics
; 16(10): 727-34, 2006 Oct.
Article
em En
| MEDLINE
| ID: mdl-17001292
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.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Haplótipos
/
Fármacos Gastrointestinais
/
Doença de Crohn
/
Fator de Necrose Tumoral alfa
/
Proteínas ADAM
/
Anticorpos Monoclonais
Limite:
Adult
/
Humans
/
Middle aged
Idioma:
En
Revista:
Pharmacogenet Genomics
Assunto da revista:
FARMACOLOGIA
/
GENETICA MEDICA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Bélgica