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

2014Journal article Open access
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dc.contributor.authorCravo, M
dc.contributor.authorFerreira, P
dc.contributor.authorSousa, P
dc.contributor.authorMoura-Santos, P
dc.contributor.authorVelho, S
dc.contributor.authorTavares, L
dc.contributor.authorDeus, JR
dc.contributor.authorMinistro, P
dc.contributor.authorSilva, J
dc.contributor.authorCorreia, L
dc.contributor.authorVelosa, J
dc.contributor.authorMaio, R
dc.contributor.authorBrito, M
dc.date.accessioned2016-04-01T14:19:25Z
dc.date.available2016-04-01T14:19:25Z
dc.date.issued2014
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.pt_PT
dc.identifier.citationUnited European Gastroenterol J. 2014 Feb;2(1):47-56pt_PT
dc.identifier.doi10.1177/2050640613519626pt_PT
dc.identifier.issn2050-6414
dc.identifier.urihttp://hdl.handle.net/10400.10/1600
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSage Publicationspt_PT
dc.relation.publisherversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040806/pdf/10.1177_2050640613519626.pdfpt_PT
dc.subjectCrohn diseasept_PT
dc.subjectDoença de Crohnpt_PT
dc.titleClinical and genetic factors predicting response to therapy in patients with Crohn's diseasept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceLondonpt_PT
oaire.citation.endPage56pt_PT
oaire.citation.startPage47pt_PT
oaire.citation.titleUnited European gastroenterology journalpt_PT
oaire.citation.volume2pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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