title: Clinical and genetic factors predicting response to therapy in patients with Crohn's disease.
abstract: OBJECTIVE
  To identify clinical and/or genetic predictors of response to several therapies in Crohn's disease (CD) patients.
  
  
  METHODS
  We included 242 patients with CD (133 females) aged (mean ± standard deviation) 39 ± 12 years and a disease duration of 12 ± 8 years. The single-nucleotide polymorphisms (SNPs) studied were ABCB1 C3435T and G2677T/A, IL23R G1142A, C2370A, and G9T, CASP9 C93T, Fas G670A and LgC844T, and ATG16L1 A898G. Genotyping was performed with real-time PCR with Taqman probes.
  
  
  RESULTS
  Older patients responded better to 5-aminosalicylic acid (5-ASA) and to azathioprine (OR 1.07, p = 0.003 and OR 1.03, p = 0.01, respectively) while younger ones responded better to biologicals (OR 0.95, p = 0.06). Previous surgery negatively influenced response to 5-ASA compounds (OR 0.25, p = 0.05), but favoured response to azathioprine (OR 2.1, p = 0.04). In respect to genetic predictors, we observed that heterozygotes for ATGL16L1 SNP had a significantly higher chance of responding to corticosteroids (OR 2.51, p = 0.04), while homozygotes for Casp9 C93T SNP had a lower chance of responding both to corticosteroids and to azathioprine (OR 0.23, p = 0.03 and OR 0.08, p = 0.02,). TT carriers of ABCB1 C3435T SNP had a higher chance of responding to azathioprine (OR 2.38, p = 0.01), while carriers of ABCB1 G2677T/A SNP, as well as responding better to azathioprine (OR 1.89, p = 0.07), had a lower chance of responding to biologicals (OR 0.31, p = 0.07), which became significant after adjusting for gender (OR 0.75, p = 0.005).
  
  
  CONCLUSIONS
  In the present study, we were able to identify a number of clinical and genetic predictors of response to several therapies which may become of potential utility in clinical practice. These are preliminary results that need to be replicated in future pharmacogenomic studies.
authors.affiliation: Hospital Beatriz Angelo, Loures, Portugal ; Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Marilia
authors.initials: M
authors.lastname: Cravo
authors.affiliation: Escola Superior de Tecnologias da Saude, Lisbon, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Ferreira
authors.affiliation: Hospital Santa Maria, Lisboa, Portugal.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sousa
authors.affiliation: Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal ; Hospital Santa Maria, Lisboa, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Moura-Santos
authors.affiliation: Hospital Beatriz Angelo, Loures, Portugal.
authors.forename: Sonia
authors.initials: S
authors.lastname: Velho
authors.affiliation: Hospital Santa Maria, Lisboa, Portugal.
authors.forename: Lurdes
authors.initials: L
authors.lastname: Tavares
authors.affiliation: Hospital Fernando da Fonseca, Amadora, Portugal.
authors.forename: João Ramos
authors.initials: JR
authors.lastname: Deus
authors.affiliation: Hospital S Teotónio, Viseu, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Ministro
authors.affiliation: Instituto Portugués de Oncologia, Lisboa, Portugal.
authors.forename: João Pereira
authors.initials: JP
authors.lastname: da Silva
authors.affiliation: Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal ; Hospital Santa Maria, Lisboa, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Correia
authors.affiliation: Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal ; Hospital Santa Maria, Lisboa, Portugal.
authors.forename: Jose
authors.initials: J
authors.lastname: Velosa
authors.affiliation: Hospital Beatriz Angelo, Loures, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Maio
authors.affiliation: Escola Superior de Tecnologias da Saude, Lisbon, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Brito
keywords: Crohn’s disease; clinical genetic predictors; response to therapy