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 sign...
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| creator | Uehara, Ryohei Yajima, Hiroyuki Chen, Chun Chuan Fukuda, Yasuhiro Takeshima, Fuminao Nakao, Kazuhiko Tsukamoto, Kazuhiro Sato, Kayoko Higuchi, Norihide Kondo, Shinji Inamine, Tatsuo Maeda, Kazumi Ishida, Tetsuya Isomoto, Hajime Urabe, Shigetoshi Machida, Haruhisa |
| 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. |
| doi_str_mv | 10.1155/2015/416838 |
| format | Article |
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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.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2015/416838</identifier><identifier>PMID: 26558270</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Adult ; Alleles ; Biomarkers ; Biomarkers - metabolism ; Crohn Disease - drug therapy ; Crohn Disease - genetics ; Crohn's disease ; Dosage and administration ; Drug therapy ; Endoscopy ; Female ; Gastroenterology ; Gastrointestinal Agents - therapeutic use ; Genetic aspects ; Genetic polymorphisms ; Genotype ; Health aspects ; Hospitals ; Humans ; Inflammatory bowel disease ; Infliximab ; Infliximab - therapeutic use ; Interleukin-17 - genetics ; International organizations ; Kinases ; Lupus ; Male ; Multiple sclerosis ; Polymorphism, Single Nucleotide - genetics ; Proteins ; Rheumatoid arthritis ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins - genetics ; Tumor necrosis factor-TNF</subject><ispartof>BioMed research international, 2015-01, Vol.2015 (2015), p.1-12</ispartof><rights>Copyright © 2015 Shigetoshi Urabe et al.</rights><rights>COPYRIGHT 2015 John Wiley & Sons, Inc.</rights><rights>Copyright © 2015 Shigetoshi Urabe et al. 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.</rights><rights>Copyright © 2015 Shigetoshi Urabe et al. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c618t-69112d6c6c2a2733a6c96c2754a4619aa9fb6c74f67e98621dfdd88e1323464a3</citedby><cites>FETCH-LOGICAL-c618t-69112d6c6c2a2733a6c96c2754a4619aa9fb6c74f67e98621dfdd88e1323464a3</cites><orcidid>0000-0001-8702-7983</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628975/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628975/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26558270$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Sakuraba, Atsushi</contributor><creatorcontrib>Uehara, Ryohei</creatorcontrib><creatorcontrib>Yajima, Hiroyuki</creatorcontrib><creatorcontrib>Chen, Chun Chuan</creatorcontrib><creatorcontrib>Fukuda, Yasuhiro</creatorcontrib><creatorcontrib>Takeshima, Fuminao</creatorcontrib><creatorcontrib>Nakao, Kazuhiko</creatorcontrib><creatorcontrib>Tsukamoto, Kazuhiro</creatorcontrib><creatorcontrib>Sato, Kayoko</creatorcontrib><creatorcontrib>Higuchi, Norihide</creatorcontrib><creatorcontrib>Kondo, Shinji</creatorcontrib><creatorcontrib>Inamine, Tatsuo</creatorcontrib><creatorcontrib>Maeda, Kazumi</creatorcontrib><creatorcontrib>Ishida, Tetsuya</creatorcontrib><creatorcontrib>Isomoto, Hajime</creatorcontrib><creatorcontrib>Urabe, Shigetoshi</creatorcontrib><creatorcontrib>Machida, Haruhisa</creatorcontrib><title>Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn’s Disease</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><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.</description><subject>Adult</subject><subject>Alleles</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Crohn Disease - drug therapy</subject><subject>Crohn Disease - genetics</subject><subject>Crohn's disease</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Endoscopy</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Gastrointestinal Agents - therapeutic use</subject><subject>Genetic aspects</subject><subject>Genetic polymorphisms</subject><subject>Genotype</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Inflammatory bowel disease</subject><subject>Infliximab</subject><subject>Infliximab - therapeutic use</subject><subject>Interleukin-17 - genetics</subject><subject>International organizations</subject><subject>Kinases</subject><subject>Lupus</subject><subject>Male</subject><subject>Multiple sclerosis</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Proteins</subject><subject>Rheumatoid arthritis</subject><subject>Tumor Necrosis Factor Receptor-Associated Peptides and Proteins - genetics</subject><subject>Tumor necrosis factor-TNF</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNks1uEzEURkcIRKvSFXtkiQ0CDR3_2xukNDQlUiQiFNaW47ETVzN2sCeF7ljyCrweT4LTlFBY1Rtb8rlH19dfVT2HzVsIKT1DDaRnBDKBxaPqGGFIagYJfHw4Y3xUneZ81ZQlIGske1odIUapQLw5rn5c2mAHb8A8djd9TJu1z30G0YHprIZ8AnRoweLTaIKncwTGcdu14NyCebKtN4O_tmCizRDTbcmwtmAWw6pe2NSDC-esGW5VwXX-m-_1EuiV9iEPYJziOvz6_jOD9z5bne2z6onTXband_tJ9XlysRh_qGcfL6fj0aw2DIqhZhJC1DLDDNKIY6yZkeXMKdGEQam1dEtmOHGMWykYgq1rWyEsxAgTRjQ-qd7tvZvtsretsWFIulObVNpLNypqr_69CX6tVvFaEYaE5LQIXt0JUvyytXlQvc_Gdp0ONm6zgpxRySWlD0ExhrIUyIK-_A-9itsUyiQKhQRrIGn4X2qlO6t8cLG0aHZSNSK0fC_EXBTqzZ4yKeacrDu8DjZqlxq1S43ap6bQL-4P5MD-yUgBXu-BtQ-t_uofZrMFsU7fgyklDcW_AX-60L0</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Uehara, Ryohei</creator><creator>Yajima, Hiroyuki</creator><creator>Chen, Chun Chuan</creator><creator>Fukuda, Yasuhiro</creator><creator>Takeshima, Fuminao</creator><creator>Nakao, Kazuhiko</creator><creator>Tsukamoto, Kazuhiro</creator><creator>Sato, Kayoko</creator><creator>Higuchi, Norihide</creator><creator>Kondo, Shinji</creator><creator>Inamine, Tatsuo</creator><creator>Maeda, Kazumi</creator><creator>Ishida, Tetsuya</creator><creator>Isomoto, Hajime</creator><creator>Urabe, Shigetoshi</creator><creator>Machida, Haruhisa</creator><general>Hindawi Publishing Corporation</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CWDGH</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8702-7983</orcidid></search><sort><creationdate>20150101</creationdate><title>Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn’s Disease</title><author>Uehara, Ryohei ; Yajima, Hiroyuki ; Chen, Chun Chuan ; Fukuda, Yasuhiro ; Takeshima, Fuminao ; Nakao, Kazuhiko ; Tsukamoto, Kazuhiro ; Sato, Kayoko ; Higuchi, Norihide ; Kondo, Shinji ; Inamine, Tatsuo ; Maeda, Kazumi ; Ishida, Tetsuya ; Isomoto, Hajime ; Urabe, Shigetoshi ; Machida, Haruhisa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c618t-69112d6c6c2a2733a6c96c2754a4619aa9fb6c74f67e98621dfdd88e1323464a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Alleles</topic><topic>Biomarkers</topic><topic>Biomarkers - metabolism</topic><topic>Crohn Disease - drug therapy</topic><topic>Crohn Disease - genetics</topic><topic>Crohn's disease</topic><topic>Dosage and administration</topic><topic>Drug therapy</topic><topic>Endoscopy</topic><topic>Female</topic><topic>Gastroenterology</topic><topic>Gastrointestinal Agents - therapeutic use</topic><topic>Genetic aspects</topic><topic>Genetic polymorphisms</topic><topic>Genotype</topic><topic>Health aspects</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Inflammatory bowel disease</topic><topic>Infliximab</topic><topic>Infliximab - therapeutic use</topic><topic>Interleukin-17 - genetics</topic><topic>International organizations</topic><topic>Kinases</topic><topic>Lupus</topic><topic>Male</topic><topic>Multiple sclerosis</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Proteins</topic><topic>Rheumatoid arthritis</topic><topic>Tumor Necrosis Factor Receptor-Associated Peptides and Proteins - genetics</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Uehara, Ryohei</creatorcontrib><creatorcontrib>Yajima, Hiroyuki</creatorcontrib><creatorcontrib>Chen, Chun Chuan</creatorcontrib><creatorcontrib>Fukuda, Yasuhiro</creatorcontrib><creatorcontrib>Takeshima, Fuminao</creatorcontrib><creatorcontrib>Nakao, Kazuhiko</creatorcontrib><creatorcontrib>Tsukamoto, Kazuhiro</creatorcontrib><creatorcontrib>Sato, Kayoko</creatorcontrib><creatorcontrib>Higuchi, Norihide</creatorcontrib><creatorcontrib>Kondo, Shinji</creatorcontrib><creatorcontrib>Inamine, Tatsuo</creatorcontrib><creatorcontrib>Maeda, Kazumi</creatorcontrib><creatorcontrib>Ishida, Tetsuya</creatorcontrib><creatorcontrib>Isomoto, Hajime</creatorcontrib><creatorcontrib>Urabe, Shigetoshi</creatorcontrib><creatorcontrib>Machida, Haruhisa</creatorcontrib><collection>الدوريات العلمية والإحصائية - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BioMed research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Uehara, Ryohei</au><au>Yajima, Hiroyuki</au><au>Chen, Chun Chuan</au><au>Fukuda, Yasuhiro</au><au>Takeshima, Fuminao</au><au>Nakao, Kazuhiko</au><au>Tsukamoto, Kazuhiro</au><au>Sato, Kayoko</au><au>Higuchi, Norihide</au><au>Kondo, Shinji</au><au>Inamine, Tatsuo</au><au>Maeda, Kazumi</au><au>Ishida, Tetsuya</au><au>Isomoto, Hajime</au><au>Urabe, Shigetoshi</au><au>Machida, Haruhisa</au><au>Sakuraba, Atsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn’s Disease</atitle><jtitle>BioMed research international</jtitle><addtitle>Biomed Res Int</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>2015</volume><issue>2015</issue><spage>1</spage><epage>12</epage><pages>1-12</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>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.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>26558270</pmid><doi>10.1155/2015/416838</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-8702-7983</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Alleles Biomarkers Biomarkers - metabolism Crohn Disease - drug therapy Crohn Disease - genetics Crohn's disease Dosage and administration Drug therapy Endoscopy Female Gastroenterology Gastrointestinal Agents - therapeutic use Genetic aspects Genetic polymorphisms Genotype Health aspects Hospitals Humans Inflammatory bowel disease Infliximab Infliximab - therapeutic use Interleukin-17 - genetics International organizations Kinases Lupus Male Multiple sclerosis Polymorphism, Single Nucleotide - genetics Proteins Rheumatoid arthritis Tumor Necrosis Factor Receptor-Associated Peptides and Proteins - genetics Tumor necrosis factor-TNF |
| title | Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn’s Disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T22%3A02%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20Polymorphisms%20of%20IL-17F%20and%20TRAF3IP2%20Could%20Be%20Predictive%20Factors%20of%20the%20Long-Term%20Effect%20of%20Infliximab%20against%20Crohn%E2%80%99s%20Disease&rft.jtitle=BioMed%20research%20international&rft.au=Uehara,%20Ryohei&rft.date=2015-01-01&rft.volume=2015&rft.issue=2015&rft.spage=1&rft.epage=12&rft.pages=1-12&rft.issn=2314-6133&rft.eissn=2314-6141&rft_id=info:doi/10.1155/2015/416838&rft_dat=%3Cgale_pubme%3EA458161378%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1728601407&rft_id=info:pmid/26558270&rft_galeid=A458161378&rfr_iscdi=true |