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Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn's Disease

Background. We aimed to identify certain genes related to response to infliximab (IFX) and biomarkers to predict the IFX effect for Japanese Crohn's disease (CD) patients by performing an association study of single nucleotide polymorphisms (SNPs) in candidate genes in the interleukin- (IL-) 17...

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Autores principales: Urabe, Shigetoshi, Isomoto, Hajime, Ishida, Tetsuya, Maeda, Kazumi, Inamine, Tatsuo, Kondo, Shinji, Higuchi, Norihide, Sato, Kayoko, Uehara, Ryohei, Yajima, Hiroyuki, Machida, Haruhisa, Chen, Chun Chuan, Fukuda, Yasuhiro, Takeshima, Fuminao, Nakao, Kazuhiko, Tsukamoto, Kazuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628975/
https://www.ncbi.nlm.nih.gov/pubmed/26558270
http://dx.doi.org/10.1155/2015/416838
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author Urabe, Shigetoshi
Isomoto, Hajime
Ishida, Tetsuya
Maeda, Kazumi
Inamine, Tatsuo
Kondo, Shinji
Higuchi, Norihide
Sato, Kayoko
Uehara, Ryohei
Yajima, Hiroyuki
Machida, Haruhisa
Chen, Chun Chuan
Fukuda, Yasuhiro
Takeshima, Fuminao
Nakao, Kazuhiko
Tsukamoto, Kazuhiro
author_facet Urabe, Shigetoshi
Isomoto, Hajime
Ishida, Tetsuya
Maeda, Kazumi
Inamine, Tatsuo
Kondo, Shinji
Higuchi, Norihide
Sato, Kayoko
Uehara, Ryohei
Yajima, Hiroyuki
Machida, Haruhisa
Chen, Chun Chuan
Fukuda, Yasuhiro
Takeshima, Fuminao
Nakao, Kazuhiko
Tsukamoto, Kazuhiro
author_sort Urabe, Shigetoshi
collection PubMed
description Background. We aimed to identify certain genes related to response to infliximab (IFX) and biomarkers to predict the IFX effect for Japanese Crohn's disease (CD) patients by performing an association study of single nucleotide polymorphisms (SNPs) in candidate genes in the interleukin- (IL-) 17 signaling pathway with response to IFX after 1 year of treatment. Methods. A total of 103 patients were divided into two groups, responders and nonresponders. Twenty-eight tag SNPs in 5 genes were genotyped. The frequencies of alleles and genotypes of each SNP were compared between responders and nonresponders in three different inheritance models. A genetic test was performed using a combination of the associated SNPs as biomarkers. Results. Multivariate logistic regression analysis indicated that the four variable factors, concomitant use of immunomodulators, penetrating disease, a G/G genotype of rs766748 in IL-17F, and a C/C or C/A genotype of rs1883136 in TRAF3IP2, independently contributed to response to IFX after 1 year of treatment. Genetic test using the polymorphisms of these genes perfectly predicted the responder and nonresponder CD patients with both concomitant use of immunomodulators and penetrating disease. Conclusion. IL17F and TRAF3IP2 are one of IFX-related genes, useful as biomarkers of IFX response, and may be target molecules for new therapeutic drugs.
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spelling pubmed-46289752015-11-10 Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn's Disease Urabe, Shigetoshi Isomoto, Hajime Ishida, Tetsuya Maeda, Kazumi Inamine, Tatsuo Kondo, Shinji Higuchi, Norihide Sato, Kayoko Uehara, Ryohei Yajima, Hiroyuki Machida, Haruhisa Chen, Chun Chuan Fukuda, Yasuhiro Takeshima, Fuminao Nakao, Kazuhiko Tsukamoto, Kazuhiro Biomed Res Int Research Article Background. We aimed to identify certain genes related to response to infliximab (IFX) and biomarkers to predict the IFX effect for Japanese Crohn's disease (CD) patients by performing an association study of single nucleotide polymorphisms (SNPs) in candidate genes in the interleukin- (IL-) 17 signaling pathway with response to IFX after 1 year of treatment. Methods. A total of 103 patients were divided into two groups, responders and nonresponders. Twenty-eight tag SNPs in 5 genes were genotyped. The frequencies of alleles and genotypes of each SNP were compared between responders and nonresponders in three different inheritance models. A genetic test was performed using a combination of the associated SNPs as biomarkers. Results. Multivariate logistic regression analysis indicated that the four variable factors, concomitant use of immunomodulators, penetrating disease, a G/G genotype of rs766748 in IL-17F, and a C/C or C/A genotype of rs1883136 in TRAF3IP2, independently contributed to response to IFX after 1 year of treatment. Genetic test using the polymorphisms of these genes perfectly predicted the responder and nonresponder CD patients with both concomitant use of immunomodulators and penetrating disease. Conclusion. IL17F and TRAF3IP2 are one of IFX-related genes, useful as biomarkers of IFX response, and may be target molecules for new therapeutic drugs. Hindawi Publishing Corporation 2015 2015-10-19 /pmc/articles/PMC4628975/ /pubmed/26558270 http://dx.doi.org/10.1155/2015/416838 Text en Copyright © 2015 Shigetoshi Urabe et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Urabe, Shigetoshi
Isomoto, Hajime
Ishida, Tetsuya
Maeda, Kazumi
Inamine, Tatsuo
Kondo, Shinji
Higuchi, Norihide
Sato, Kayoko
Uehara, Ryohei
Yajima, Hiroyuki
Machida, Haruhisa
Chen, Chun Chuan
Fukuda, Yasuhiro
Takeshima, Fuminao
Nakao, Kazuhiko
Tsukamoto, Kazuhiro
Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn's Disease
title Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn's Disease
title_full Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn's Disease
title_fullStr Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn's Disease
title_full_unstemmed Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn's Disease
title_short Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn's Disease
title_sort genetic polymorphisms of il-17f and traf3ip2 could be predictive factors of the long-term effect of infliximab against crohn's disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628975/
https://www.ncbi.nlm.nih.gov/pubmed/26558270
http://dx.doi.org/10.1155/2015/416838
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