Marilia Cravo1, Paula Ferreira2, Patricia Sousa3, Paula Moura-Santos4, Sonia Velho5, Lurdes Tavares3, João Ramos Deus6, Paula Ministro7, João Pereira da Silva8, Luis Correia4, Jose Velosa4, Rui Maio5, Miguel Brito2. 1. Hospital Beatriz Angelo, Loures, Portugal ; Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal. 2. Escola Superior de Tecnologias da Saude, Lisbon, Portugal. 3. Hospital Santa Maria, Lisboa, Portugal. 4. Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal ; Hospital Santa Maria, Lisboa, Portugal. 5. Hospital Beatriz Angelo, Loures, Portugal. 6. Hospital Fernando da Fonseca, Amadora, Portugal. 7. Hospital S Teotónio, Viseu, Portugal. 8. Instituto Portugués de Oncologia, Lisboa, Portugal.
Abstract
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.
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 ABCB1C3435T and G2677T/A, IL23RG1142A, C2370A, and G9T, CASP9C93T, FasG670A and LgC844T, and ATG16L1A898G. 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 Casp9C93T 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 ABCB1C3435T SNP had a higher chance of responding to azathioprine (OR 2.38, p = 0.01), while carriers of ABCB1G2677T/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.
Entities:
Keywords:
Crohn’s disease; clinical genetic predictors; response to therapy
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