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EnglishAnti-tumor necrosis factor agents have become the mainstay of treatment in refractory inflammatory bowel diseases (IBD), also in pediatric patients. Currently, there are no predictors of response to therapy. The aim of the present study was to evaluate the role of polymorphisms in the promoter region of the IL6 gene (−174G/C−rs1800795) and of the TNF gene (−308A/G −rs1800629) on the response to infliximab in an Italian cohort of children and young adults with IBD. Patients were enrolled at Institute for Maternal and Child health IRCCS “Burlo Garofolo” in Trieste, Italy; clinical data were collected retrospectively. Response to infliximab was defined as a decrease in disease activity scores of at least 15 points after induction therapy, and as the need to switch therapy before 12 months. SNPs were characterized by PCR-RFLP assays on DNA from peripheral blood. Sixty-four patients with IBD (65.6% Crohn’s disease, 34.4% ulcerative colitis) were enrolled. 21.9% did not respond to induction therapy, and 36.8% had to switch therapy before 12 months. Genotyping analysis identified a significant association between the homozygous CC variant of the −174G/C IL6 polymorphism and a diminished response to induction therapy: frequency of non-response in patients with this genotype was three times that of patients with GG/GC genotype (p < 0.05). No correlation was found with the TNF polymorphism. This is the first study evaluating the effect of pharmacogenetic variants in Italian patients with pediatric IBD, yet it should be further validated by larger prospective studies.
| Titolo: | Pharmacogenetic determinants of response to infliximab in pediatric inflammatory bowel disease | |
| Autori: | ||
| Data di pubblicazione: | 2015 | |
| Rivista: | ||
| Abstract: | Anti-tumor necrosis factor agents have become the mainstay of treatment in refractory inflammatory bowel diseases (IBD), also in pediatric patients. Currently, there are no predictors of response to therapy. The aim of the present study was to evaluate the role of polymorphisms in the promoter region of the IL6 gene (−174G/C−rs1800795) and of the TNF gene (−308A/G −rs1800629) on the response to infliximab in an Italian cohort of children and young adults with IBD. Patients were enrolled at Institute for Maternal and Child health IRCCS “Burlo Garofolo” in Trieste, Italy; clinical data were collected retrospectively. Response to infliximab was defined as a decrease in disease activity scores of at least 15 points after induction therapy, and as the need to switch therapy before 12 months. SNPs were characterized by PCR-RFLP assays on DNA from peripheral blood. Sixty-four patients with IBD (65.6% Crohn’s disease, 34.4% ulcerative colitis) were enrolled. 21.9% did not respond to induction therapy, and 36.8% had to switch therapy before 12 months. Genotyping analysis identified a significant association between the homozygous CC variant of the −174G/C IL6 polymorphism and a diminished response to induction therapy: frequency of non-response in patients with this genotype was three times that of patients with GG/GC genotype (p < 0.05). No correlation was found with the TNF polymorphism. This is the first study evaluating the effect of pharmacogenetic variants in Italian patients with pediatric IBD, yet it should be further validated by larger prospective studies. | |
| Handle: | http://hdl.handle.net/11368/2883880 | |
| URL: | http://www.dldjournalonline.com/issue/S1590-8658(15)X0011-9 | |
| Appare nelle tipologie: | 4.1 Contributo in Atti Convegno (Proceeding) |
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