Confirmation of −174G/C interleukin-6 gene promoter polymorphism as a genetic marker predicting antitumor necrosis factor treatment outcome
BACKGROUNDThe IL-6 –174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis fa...
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| Veröffentlicht in: | Pharmacogenetics and genomics 2014-01, Vol.24 (1), p.1-5 |
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| creator | Dávila-Fajardo, Cristina L Márquez, Ana Pascual-Salcedo, Dora Moreno Ramos, Manuel J García-Portales, Rosa Magro, César Alegre-Sancho, Juan J Balsa, Alejandro Cabeza-Barrera, José Raya, Enrique Martín, Javier |
| description | BACKGROUNDThe IL-6 –174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA.
MATERIALS AND METHODSOur study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 –174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion.
RESULTSThe −174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29–6.70], 18 (P=4.54E−03, OR=5.17, 95% CI 1.80–14.85), and 24 months (P=4.54E−03, OR=14.86, 95% CI 2.91–75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E−02, OR=1.80, 95% CI 1.13–2.87, at 12 months).
CONCLUSIONOur results support the role of the −174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy. |
| doi_str_mv | 10.1097/FPC.0000000000000013 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1467064661</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1467064661</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4073-a0c0cbd92d89e3e4341b60b711b59e55902e5a817ffafd5b59af74523ade00c63</originalsourceid><addsrcrecordid>eNp9kcFu3CAQhlHUqtlu-gZVxbEXZ8HG2D5GVjatFKk9NGcL42GXrIENYK32DXLJJY-YJynbTSMlh3CBGb5_YOZH6Csl55Q01WL5uz0nrxYtTtCMVoxlvK7Jh5dzlZ-izyHcElLwhuWf0GnO8rIoGzZDD62zSnsjonYWO4Wf7h-T7GrRYm0j-BGmjbYZxyuwgLfeGZeyeOvGvXF-u9bBYBGw-HcftcRG-M0B8DBoGbVdYWGjjlOisQXpXdABKyFjiqMHEQ3YiN0UpTNwhj4qMQb48rzP0c3y8k_7I7v-dfWzvbjOJCNVkQkiieyHJh_qBgpgBaM9J31FaV82UJYNyaEUNa2UEmooU1KoipV5IQYgRPJijr4f66aG7iYIsTM6SBhHYcFNoaOMV4QzzmlC2RE9fD14UN3W69TkvqOkOxjRJSO6t0Yk2bfnF6bewPAi-j_5BNRHYOfGNNGwGacd-G4NYozr92v_BSK9mAo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1467064661</pqid></control><display><type>article</type><title>Confirmation of −174G/C interleukin-6 gene promoter polymorphism as a genetic marker predicting antitumor necrosis factor treatment outcome</title><source>Journals@Ovid Ovid Autoload</source><source>MEDLINE</source><creator>Dávila-Fajardo, Cristina L ; Márquez, Ana ; Pascual-Salcedo, Dora ; Moreno Ramos, Manuel J ; García-Portales, Rosa ; Magro, César ; Alegre-Sancho, Juan J ; Balsa, Alejandro ; Cabeza-Barrera, José ; Raya, Enrique ; Martín, Javier</creator><creatorcontrib>Dávila-Fajardo, Cristina L ; Márquez, Ana ; Pascual-Salcedo, Dora ; Moreno Ramos, Manuel J ; García-Portales, Rosa ; Magro, César ; Alegre-Sancho, Juan J ; Balsa, Alejandro ; Cabeza-Barrera, José ; Raya, Enrique ; Martín, Javier</creatorcontrib><description>BACKGROUNDThe IL-6 –174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA.
MATERIALS AND METHODSOur study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 –174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion.
RESULTSThe −174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29–6.70], 18 (P=4.54E−03, OR=5.17, 95% CI 1.80–14.85), and 24 months (P=4.54E−03, OR=14.86, 95% CI 2.91–75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E−02, OR=1.80, 95% CI 1.13–2.87, at 12 months).
CONCLUSIONOur results support the role of the −174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.</description><identifier>ISSN: 1744-6872</identifier><identifier>EISSN: 1744-6880</identifier><identifier>DOI: 10.1097/FPC.0000000000000013</identifier><identifier>PMID: 24253594</identifier><language>eng</language><publisher>United States: Wolters Kluwer Health | Lippincott Williams & Wilkins</publisher><subject>Adalimumab ; Adult ; Aged ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antirheumatic Agents - administration & dosage ; Antirheumatic Agents - therapeutic use ; Arthritis, Rheumatoid - drug therapy ; Arthritis, Rheumatoid - genetics ; Cytosine ; Etanercept ; Female ; Genetic Markers ; Genotype ; Guanine ; Humans ; Immunoglobulin G - administration & dosage ; Immunoglobulin G - therapeutic use ; Infliximab ; Interleukin-6 - genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Receptors, Tumor Necrosis Factor - administration & dosage ; Receptors, Tumor Necrosis Factor - therapeutic use ; Reproducibility of Results ; Treatment Outcome ; Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><ispartof>Pharmacogenetics and genomics, 2014-01, Vol.24 (1), p.1-5</ispartof><rights>2014 Wolters Kluwer Health | Lippincott Williams & Wilkins</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4073-a0c0cbd92d89e3e4341b60b711b59e55902e5a817ffafd5b59af74523ade00c63</citedby><cites>FETCH-LOGICAL-c4073-a0c0cbd92d89e3e4341b60b711b59e55902e5a817ffafd5b59af74523ade00c63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24253594$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dávila-Fajardo, Cristina L</creatorcontrib><creatorcontrib>Márquez, Ana</creatorcontrib><creatorcontrib>Pascual-Salcedo, Dora</creatorcontrib><creatorcontrib>Moreno Ramos, Manuel J</creatorcontrib><creatorcontrib>García-Portales, Rosa</creatorcontrib><creatorcontrib>Magro, César</creatorcontrib><creatorcontrib>Alegre-Sancho, Juan J</creatorcontrib><creatorcontrib>Balsa, Alejandro</creatorcontrib><creatorcontrib>Cabeza-Barrera, José</creatorcontrib><creatorcontrib>Raya, Enrique</creatorcontrib><creatorcontrib>Martín, Javier</creatorcontrib><title>Confirmation of −174G/C interleukin-6 gene promoter polymorphism as a genetic marker predicting antitumor necrosis factor treatment outcome</title><title>Pharmacogenetics and genomics</title><addtitle>Pharmacogenet Genomics</addtitle><description>BACKGROUNDThe IL-6 –174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA.
MATERIALS AND METHODSOur study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 –174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion.
RESULTSThe −174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29–6.70], 18 (P=4.54E−03, OR=5.17, 95% CI 1.80–14.85), and 24 months (P=4.54E−03, OR=14.86, 95% CI 2.91–75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E−02, OR=1.80, 95% CI 1.13–2.87, at 12 months).
CONCLUSIONOur results support the role of the −174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.</description><subject>Adalimumab</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Antirheumatic Agents - administration & dosage</subject><subject>Antirheumatic Agents - therapeutic use</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Arthritis, Rheumatoid - genetics</subject><subject>Cytosine</subject><subject>Etanercept</subject><subject>Female</subject><subject>Genetic Markers</subject><subject>Genotype</subject><subject>Guanine</subject><subject>Humans</subject><subject>Immunoglobulin G - administration & dosage</subject><subject>Immunoglobulin G - therapeutic use</subject><subject>Infliximab</subject><subject>Interleukin-6 - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Promoter Regions, Genetic</subject><subject>Receptors, Tumor Necrosis Factor - administration & dosage</subject><subject>Receptors, Tumor Necrosis Factor - therapeutic use</subject><subject>Reproducibility of Results</subject><subject>Treatment Outcome</subject><subject>Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><issn>1744-6872</issn><issn>1744-6880</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFu3CAQhlHUqtlu-gZVxbEXZ8HG2D5GVjatFKk9NGcL42GXrIENYK32DXLJJY-YJynbTSMlh3CBGb5_YOZH6Csl55Q01WL5uz0nrxYtTtCMVoxlvK7Jh5dzlZ-izyHcElLwhuWf0GnO8rIoGzZDD62zSnsjonYWO4Wf7h-T7GrRYm0j-BGmjbYZxyuwgLfeGZeyeOvGvXF-u9bBYBGw-HcftcRG-M0B8DBoGbVdYWGjjlOisQXpXdABKyFjiqMHEQ3YiN0UpTNwhj4qMQb48rzP0c3y8k_7I7v-dfWzvbjOJCNVkQkiieyHJh_qBgpgBaM9J31FaV82UJYNyaEUNa2UEmooU1KoipV5IQYgRPJijr4f66aG7iYIsTM6SBhHYcFNoaOMV4QzzmlC2RE9fD14UN3W69TkvqOkOxjRJSO6t0Yk2bfnF6bewPAi-j_5BNRHYOfGNNGwGacd-G4NYozr92v_BSK9mAo</recordid><startdate>201401</startdate><enddate>201401</enddate><creator>Dávila-Fajardo, Cristina L</creator><creator>Márquez, Ana</creator><creator>Pascual-Salcedo, Dora</creator><creator>Moreno Ramos, Manuel J</creator><creator>García-Portales, Rosa</creator><creator>Magro, César</creator><creator>Alegre-Sancho, Juan J</creator><creator>Balsa, Alejandro</creator><creator>Cabeza-Barrera, José</creator><creator>Raya, Enrique</creator><creator>Martín, Javier</creator><general>Wolters Kluwer Health | Lippincott Williams & Wilkins</general><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>7X8</scope></search><sort><creationdate>201401</creationdate><title>Confirmation of −174G/C interleukin-6 gene promoter polymorphism as a genetic marker predicting antitumor necrosis factor treatment outcome</title><author>Dávila-Fajardo, Cristina L ; Márquez, Ana ; Pascual-Salcedo, Dora ; Moreno Ramos, Manuel J ; García-Portales, Rosa ; Magro, César ; Alegre-Sancho, Juan J ; Balsa, Alejandro ; Cabeza-Barrera, José ; Raya, Enrique ; Martín, Javier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4073-a0c0cbd92d89e3e4341b60b711b59e55902e5a817ffafd5b59af74523ade00c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adalimumab</topic><topic>Adult</topic><topic>Aged</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Antirheumatic Agents - administration & dosage</topic><topic>Antirheumatic Agents - therapeutic use</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Arthritis, Rheumatoid - genetics</topic><topic>Cytosine</topic><topic>Etanercept</topic><topic>Female</topic><topic>Genetic Markers</topic><topic>Genotype</topic><topic>Guanine</topic><topic>Humans</topic><topic>Immunoglobulin G - administration & dosage</topic><topic>Immunoglobulin G - therapeutic use</topic><topic>Infliximab</topic><topic>Interleukin-6 - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Promoter Regions, Genetic</topic><topic>Receptors, Tumor Necrosis Factor - administration & dosage</topic><topic>Receptors, Tumor Necrosis Factor - therapeutic use</topic><topic>Reproducibility of Results</topic><topic>Treatment Outcome</topic><topic>Tumor Necrosis Factor-alpha - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dávila-Fajardo, Cristina L</creatorcontrib><creatorcontrib>Márquez, Ana</creatorcontrib><creatorcontrib>Pascual-Salcedo, Dora</creatorcontrib><creatorcontrib>Moreno Ramos, Manuel J</creatorcontrib><creatorcontrib>García-Portales, Rosa</creatorcontrib><creatorcontrib>Magro, César</creatorcontrib><creatorcontrib>Alegre-Sancho, Juan J</creatorcontrib><creatorcontrib>Balsa, Alejandro</creatorcontrib><creatorcontrib>Cabeza-Barrera, José</creatorcontrib><creatorcontrib>Raya, Enrique</creatorcontrib><creatorcontrib>Martín, Javier</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacogenetics and genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dávila-Fajardo, Cristina L</au><au>Márquez, Ana</au><au>Pascual-Salcedo, Dora</au><au>Moreno Ramos, Manuel J</au><au>García-Portales, Rosa</au><au>Magro, César</au><au>Alegre-Sancho, Juan J</au><au>Balsa, Alejandro</au><au>Cabeza-Barrera, José</au><au>Raya, Enrique</au><au>Martín, Javier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Confirmation of −174G/C interleukin-6 gene promoter polymorphism as a genetic marker predicting antitumor necrosis factor treatment outcome</atitle><jtitle>Pharmacogenetics and genomics</jtitle><addtitle>Pharmacogenet Genomics</addtitle><date>2014-01</date><risdate>2014</risdate><volume>24</volume><issue>1</issue><spage>1</spage><epage>5</epage><pages>1-5</pages><issn>1744-6872</issn><eissn>1744-6880</eissn><abstract>BACKGROUNDThe IL-6 –174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA.
MATERIALS AND METHODSOur study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 –174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion.
RESULTSThe −174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29–6.70], 18 (P=4.54E−03, OR=5.17, 95% CI 1.80–14.85), and 24 months (P=4.54E−03, OR=14.86, 95% CI 2.91–75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E−02, OR=1.80, 95% CI 1.13–2.87, at 12 months).
CONCLUSIONOur results support the role of the −174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.</abstract><cop>United States</cop><pub>Wolters Kluwer Health | Lippincott Williams & Wilkins</pub><pmid>24253594</pmid><doi>10.1097/FPC.0000000000000013</doi><tpages>5</tpages></addata></record> |
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| subjects | Adalimumab Adult Aged Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Humanized - therapeutic use Antirheumatic Agents - administration & dosage Antirheumatic Agents - therapeutic use Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - genetics Cytosine Etanercept Female Genetic Markers Genotype Guanine Humans Immunoglobulin G - administration & dosage Immunoglobulin G - therapeutic use Infliximab Interleukin-6 - genetics Male Middle Aged Polymorphism, Single Nucleotide Promoter Regions, Genetic Receptors, Tumor Necrosis Factor - administration & dosage Receptors, Tumor Necrosis Factor - therapeutic use Reproducibility of Results Treatment Outcome Tumor Necrosis Factor-alpha - antagonists & inhibitors |
| title | Confirmation of −174G/C interleukin-6 gene promoter polymorphism as a genetic marker predicting antitumor necrosis factor treatment outcome |
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