Publicação
IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis.
| Resumo: | 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. |
|---|---|
| Autores principais: | Cravo, M |
| Outros Autores: | Ferreira, P; Sousa, P; Moura-Santos, P; Velho, S; Tavares, L; Deus, JR; Ministro, P; Peixe, P; Correia, L; Velosa, J; Maio, R; Brito, M |
| Assunto: | Ulcerative colitis Anti-Inflammatory agents Colite ulcerosa Anti-inflamatórios |
| Ano: | 2014 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Hospital Prof. Dr. Fernando Fonseca E.P.E. |
| Idioma: | inglês |
| Origem: | Repositório do Hospital Prof. Doutor Fernando Fonseca |
| _version_ | 1868417263048065024 |
|---|---|
| author | Cravo, M |
| author2 | Ferreira, P Sousa, P Moura-Santos, P Velho, S Tavares, L Deus, JR Ministro, P Peixe, P Correia, L Velosa, J Maio, R Brito, M |
| author2_role | author author author author author author author author author author author author |
| author_facet | Cravo, M Ferreira, P Sousa, P Moura-Santos, P Velho, S Tavares, L Deus, JR Ministro, P Peixe, P Correia, L Velosa, J Maio, R Brito, M |
| author_role | author |
| contributor_name_str_mv | Unidade Local de Saúde Amadora / Sintra |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Cravo, M\"},{\"Person.name\":\"Ferreira, P\"},{\"Person.name\":\"Sousa, P\"},{\"Person.name\":\"Moura-Santos, P\"},{\"Person.name\":\"Velho, S\"},{\"Person.name\":\"Tavares, L\"},{\"Person.name\":\"Deus, JR\"},{\"Person.name\":\"Ministro, P\"},{\"Person.name\":\"Peixe, P\"},{\"Person.name\":\"Correia, L\"},{\"Person.name\":\"Velosa, J\"},{\"Person.name\":\"Maio, R\"},{\"Person.name\":\"Brito, M\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Unidade Local de Saúde Amadora / Sintra |
| datacite.creators.creator.creatorName.fl_str_mv | Cravo, M Ferreira, P Sousa, P Moura-Santos, P Velho, S Tavares, L Deus, JR Ministro, P Peixe, P Correia, L Velosa, J Maio, R Brito, M |
| datacite.date.Accepted.fl_str_mv | 2014-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2015-01-23T15:12:06Z |
| datacite.date.embargoed.fl_str_mv | 2015-01-23T15:12:06Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| datacite.subjects.subject.fl_str_mv | Ulcerative colitis Anti-Inflammatory agents Colite ulcerosa Anti-inflamatórios |
| datacite.titles.title.fl_str_mv | IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis. |
| dc.contributor.none.fl_str_mv | Unidade Local de Saúde Amadora / Sintra |
| dc.creator.none.fl_str_mv | Cravo, M Ferreira, P Sousa, P Moura-Santos, P Velho, S Tavares, L Deus, JR Ministro, P Peixe, P Correia, L Velosa, J Maio, R Brito, M |
| dc.date.Accepted.fl_str_mv | 2014-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2015-01-23T15:12:06Z |
| dc.date.embargoed.fl_str_mv | 2015-01-23T15:12:06Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10400.10/1344 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Lippincott Williams And Wilkins |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| dc.subject.none.fl_str_mv | Ulcerative colitis Anti-Inflammatory agents Colite ulcerosa Anti-inflamatórios |
| dc.title.fl_str_mv | IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis. |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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. |
| dirty | 0 |
| eu_rights_str_mv | restrictedAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.hff.min-saude.pt/bitstreams/7696d362-95a5-4dea-a64e-bf0b3cd9a8d0/download |
| id | rhff_7fcddf62b5ea4dd5e0f4e7ac63d16a14 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10400.10/1344 |
| instacron_str | hff |
| institution | Hospital Prof. Dr. Fernando Fonseca E.P.E. |
| instname_str | Hospital Prof. Dr. Fernando Fonseca E.P.E. |
| language | eng |
| network_acronym_str | rhff |
| network_name_str | Repositório do Hospital Prof. Doutor Fernando Fonseca |
| oai_identifier_str | oai:repositorio.hff.min-saude.pt:10400.10/1344 |
| organization_str_mv | urn:organizationAcronym:hff |
| person_str_mv | Cravo, M Ferreira, P Sousa, P Moura-Santos, P Velho, S Tavares, L Deus, JR Ministro, P Peixe, P Correia, L Velosa, J Maio, R Brito, M |
| publishDate | 2014 |
| publisher.none.fl_str_mv | Lippincott Williams And Wilkins |
| reponame_str | Repositório do Hospital Prof. Doutor Fernando Fonseca |
| repository_id_str | urn:repositoryAcronym:rhff |
| service_str_mv | urn:repositoryAcronym:rhff |
| spelling | engLippincott Williams And WilkinsporOBJECTIVE: 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.application/pdfporIL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis.Cravo, MFerreira, PSousa, PMoura-Santos, PVelho, STavares, LDeus, JRMinistro, PPeixe, PCorreia, LVelosa, JMaio, RBrito, MHostingInstitutionOrganizationalUnidade Local de Saúde Amadora / Sintrae-mailmailto:repositorio@hff.min-saude.ptrepositorio@hff.min-saude.ptDOIIsPartOf10.1097/MEG.00000000000000042015-01-23T15:12:06Z20142014-01-01T00:00:00ZHandlehttp://hdl.handle.net/10400.10/1344http://purl.org/coar/access_right/c_16ecrestricted accessUlcerative colitisAnti-Inflammatory agentsColite ulcerosaAnti-inflamatórios363928 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorio.hff.min-saude.pt/bitstreams/7696d362-95a5-4dea-a64e-bf0b3cd9a8d0/downloadEuropean Journal of Gastroenterology and Hepatology262632London |
| spellingShingle | IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis. Cravo, M Ulcerative colitis Anti-Inflammatory agents Colite ulcerosa Anti-inflamatórios |
| status | SINGLETON |
| subject.fl_str_mv | Ulcerative colitis Anti-Inflammatory agents Colite ulcerosa Anti-inflamatórios |
| title | IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis. |
| title_full | IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis. |
| title_fullStr | IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis. |
| title_full_unstemmed | IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis. |
| title_short | IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis. |
| title_sort | IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis. |
| topic | Ulcerative colitis Anti-Inflammatory agents Colite ulcerosa Anti-inflamatórios |
| topic_facet | Ulcerative colitis Anti-Inflammatory agents Colite ulcerosa Anti-inflamatórios |
| url | http://hdl.handle.net/10400.10/1344 |
| visible | 1 |