title: Lymphotoxin alpha gene in Crohn's disease patients: absence of implication in the response to infliximab in a large cohort study.
abstract: A haplotype in the lymphotoxin alpha (LTA) gene has been associated with a lack of response to infliximab in a small cohort of Crohn's disease (CD) patients. The present study aimed to confirm the implication of this haplotype in the response to infliximab in a larger cohort of Caucasian patients. The response to the first infusion with infliximab was evaluated in 214 Caucasian patients with either luminal (n=150) or fistulising (n=64) CD. Clinical response was based on the decrease in CD Activity Index (luminal) or on the evolution in the fistula discharge (fistulising). Biological response was assessed in 139 patients who had elevated C-reactive protein (CRP) before treatment and for whom CRP values were also available after treatment. A positive biological response was defined as a decrease in CRP of at least 25%. The patients were genotyped for six polymorphisms in the LTA gene. A positive clinical response was present in 65.4% of the patients and a positive biological response was observed in 80.6% of the patients. No association was found with any of the studied polymorphisms, nor with the previously published LTA haplotype and the response to infliximab. We could not confirm an association between the LTA locus and clinical or biological response to infliximab in a large cohort of CD patients.
authors.affiliation: Department of Human Genetics, CHU Sart-Tilman, University of Liège, 4000 Liège, Belgium.
authors.forename: Vinciane
authors.initials: V
authors.lastname: Dideberg
authors.forename: Edouard
authors.initials: E
authors.lastname: Louis
authors.forename: Frédéric
authors.initials: F
authors.lastname: Farnir
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bertoli
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: Martine
authors.initials: M
authors.lastname: De Vos
authors.forename: André
authors.initials: A
authors.lastname: Van Gossum
authors.forename: Jacques
authors.initials: J
authors.lastname: Belaiche
authors.forename: Vincent
authors.initials: V
authors.lastname: Bours
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D003424:Crohn Disease / Q000097:blood / Q000235:genetics / Q000628:therapy*; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006239:Haplotypes; D006801:Humans; D000069285:Infliximab; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D044465:White People
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D008233:Lymphotoxin-alpha; D002097:C-Reactive Protein; D000069285:Infliximab