Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.21/3452
Título: Clinical and genetic factors predicting response to therapy in patients with Crohn’s disease
Autor: Cravo, Marília
Ferreira, Paula
Sousa, Patrícia
Moura-Santos, Paula
Velho, Sónia
Tavares, Lurdes
Deus, João Ramos
Ministro, Paula
Silva, João Pereira da
Correia, Luís
Velosa, José
Maio, Rui
Brito, Miguel
Palavras-chave: Crohn’s disease
Clinical genetic predictors
Response to therapy
Chronic disease
Data: Mar-2014
Editora: Sage
Citação: Cravo 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.
Resumo: Aim - 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.
Peer review: yes
URI: http://hdl.handle.net/10400.21/3452
Versão do Editor: http://ueg.sagepub.com/content/2/1/47.abstract
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