title: IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis.
abstract: OBJECTIVE
  We aimed to identify the clinical and genetic [IL23 receptor (IL23R) single nucleotide polymorphisms (SNPs)] predictors of response to therapy in patients with ulcerative colitis.
  
  
  METHODS
  A total of 174 patients with ulcerative colitis, 99 women and 75 men, were included. The mean age of the patients was 47±15 years and the mean disease duration was 11±9 years. The number of patients classified as responders (R) or nonresponders (NR) to several therapies was as follows: 110 R and 53 NR to mesalazine (5-ASA), 28 R and 20 NR to azathioprine (AZT), 18 R and 7 NR to infliximab. Clinical and demographic variables were recorded. A total of four SNPs were studied: IL23R G1142A, C2370A, G43045A, and G9T. Genotyping was performed by real-time PCR using Taqman probes.
  
  
  RESULTS
  Older patients were more prone to respond to 5-ASA (P=0.004), whereas those with pancolitis were less likely to respond to such therapies (P=0.002). Patients with extraintestinal manifestations (EIMs) were less likely to respond to 5-ASA (P=0.001), AZT (P=0.03), and corticosteroids (P=0.06). Carriers of the mutant allele for IL23R SNPs had a significantly higher probability of developing EIMs (P<0.05), a higher probability of being refractory to 5-ASA (P<0.03), but a higher likelihood of responding to AZT (P=0.05). A significant synergism was observed between IL23R C2370A and EIMs with respect to nonresponse to 5-ASA (P=0.03).
  
  
  CONCLUSIONS
  Besides extent of disease and age at disease onset, the presence of EIMs may be a marker of refractoriness to 5-ASA, corticosteroids, and AZT. IL23R SNPs are associated both with EIMs and with nonresponse to 5-ASA and corticosteroids.
authors.affiliation: aGastroenterology Service bDietetics Service, Beatriz Angelo Hospital, Loures cFaculty of Medicine, Lisbon University dDepartment of Natural Sciences, School of Health Technologies eGastroenterology Service, Santa Maria Hospital fGastroenterology Service, Egas Moniz Hospital, Lisbon gGastroenterology Service, Fernando da Fonseca Hospital, Amadora hGastroenterology Service, S. Teotónio Hospital, Viseu, Portuga.
authors.forename: Marília L
authors.initials: ML
authors.lastname: Cravo
authors.forename: Paula A
authors.initials: PA
authors.lastname: Ferreira
authors.forename: Patricia
authors.initials: P
authors.lastname: Sousa
authors.forename: Paula
authors.initials: P
authors.lastname: Moura-Santos
authors.forename: Sónia
authors.initials: S
authors.lastname: Velho
authors.forename: Lurdes
authors.initials: L
authors.lastname: Tavares
authors.forename: João R
authors.initials: JR
authors.lastname: de Deus
authors.forename: Paula
authors.initials: P
authors.lastname: Ministro
authors.forename: Paula
authors.initials: P
authors.lastname: Peixe
authors.forename: Luis A
authors.initials: LA
authors.lastname: Correia
authors.forename: José F
authors.initials: JF
authors.lastname: Velosa
authors.forename: Rui F
authors.initials: RF
authors.lastname: Maio
authors.forename: Miguel
authors.initials: M
authors.lastname: Brito
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D020022:Genetic Predisposition to Disease; D006801:Humans; D000069285:Infliximab; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D018123:Receptors, Interleukin / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; C515500:IL23R protein, human; D018123:Receptors, Interleukin; D019804:Mesalamine; D000069285:Infliximab; D001379:Azathioprine