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Clinical and genetic factors predicting response to therapy in patients with Crohn’s disease

2014-03Journal article Open access
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dc.contributor.authorCravo, Marília
dc.contributor.authorFerreira, Paula
dc.contributor.authorSousa, Patrícia
dc.contributor.authorMoura-Santos, Paula
dc.contributor.authorVelho, Sónia
dc.contributor.authorTavares, Lurdes
dc.contributor.authorDeus, João Ramos
dc.contributor.authorMinistro, Paula
dc.contributor.authorSilva, João Pereira da
dc.contributor.authorCorreia, Luís
dc.contributor.authorVelosa, José
dc.contributor.authorMaio, Rui
dc.contributor.authorBrito, Miguel
dc.date.accessioned2014-04-15T15:33:18Z
dc.date.available2014-04-15T15:33:18Z
dc.date.issued2014-03
dc.description.abstractAim - 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.por
dc.identifier.citationCravo M, Ferreira P, Sousa P, Moura-Santos P, Velho S, Brito M, et al. Clinical and genetic factors predicting response to therapy in patients with Crohn’s disease. United European Gastroenterol J. 2014;2(1):47-56.por
dc.identifier.otherDOI: 10.1177/2050640613519626
dc.identifier.urihttp://hdl.handle.net/10400.21/3452
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherSagepor
dc.relation.publisherversionhttp://ueg.sagepub.com/content/2/1/47.abstractpor
dc.subjectCrohn’s diseasepor
dc.subjectClinical genetic predictorspor
dc.subjectResponse to therapypor
dc.subjectChronic diseasepor
dc.titleClinical and genetic factors predicting response to therapy in patients with Crohn’s diseasepor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage56por
oaire.citation.startPage47por
oaire.citation.titleUnited Europeam Gastroenterology Journalpor
oaire.citation.volume2por
person.familyNameBrito
person.givenNameMiguel
person.identifier.ciencia-id231F-F341-7E93
person.identifier.orcid0000-0001-6394-658X
person.identifier.ridA-7970-2016
person.identifier.scopus-author-id35224551000
rcaap.rightsopenAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublication4252d8e0-800c-4d67-8b13-0b711d860669
relation.isAuthorOfPublication.latestForDiscovery4252d8e0-800c-4d67-8b13-0b711d860669

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