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Eur J Gastroenterol Hepatol. 2014 Jan;26(1):26-32. doi: 10.1097/MEG.0000000000000004.

IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis.

Author information

1
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.

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.

PATIENTS AND 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).

CONCLUSION:

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.

PMID:
24168842
DOI:
10.1097/MEG.0000000000000004
[Indexed for MEDLINE]
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