{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:42:22Z","timestamp":1761597742704,"version":"3.37.3"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mexican Institute for Social Security","award":["FIS\/IMSS\/PROT\/G13\/1201"],"award-info":[{"award-number":["FIS\/IMSS\/PROT\/G13\/1201"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p><jats:italic>Objective<\/jats:italic>. To evaluate the association of -174G\/C<jats:italic>IL-6<\/jats:italic>polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped for<jats:italic>IL-6<\/jats:italic>-174G\/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 &lt; 3.2).<jats:italic>Results<\/jats:italic>. Patients with MTX or LEF had significant decrement in DAS-28 (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn fontstyle=\"italic\">0.001<\/mml:mn><\/mml:math>); nevertheless, only 14% and 12.5% achieved DAS-28 &lt; 3.2 at 3 and 6 months. After 6 months with any of these drugs the -174G\/G genotype carriers (56%) had higher risk of therapeutic failure compared with GC (RR: 1.19, 95% CI: 1.07\u20131.56). By analyzing each drug separately, after 6 months with LEF, GG genotype confers higher risk of therapeutic failure than GC (RR = 1.56; 95% CI = 1.05\u20132.3;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn fontstyle=\"italic\">0.003<\/mml:mn><\/mml:math>), or CC (RR = 1.83; 95% CI = 1.07\u20133.14;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn fontstyle=\"italic\">0.001<\/mml:mn><\/mml:math>). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03\u20131.72;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn fontstyle=\"italic\">0.02<\/mml:mn><\/mml:math>). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded that<jats:italic>IL-6<\/jats:italic>-174G\/G genotype confers higher risk of failure in therapeutic response to LEF in Mexicans and if confirmed in other populations this can be used as promissory genetic marker to differentiate risk of therapeutic failure to LEF.<\/jats:p>","DOI":"10.1155\/2016\/4193538","type":"journal-article","created":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T17:04:11Z","timestamp":1474477451000},"page":"1-10","source":"Crossref","is-referenced-by-count":6,"title":["The -174G\/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis"],"prefix":"10.1155","volume":"2016","author":[{"given":"A. J.","family":"Ruiz-Padilla","sequence":"first","affiliation":[{"name":"Departamento de Medicina Interna-Reumatolog\u00eda, Hospital General Regional 110, IMSS, 44710 Guadalajara, JAL, Mexico"},{"name":"Doctorado en Farmacolog\u00eda, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (U de G), 44340 Guadalajara, JAL, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0001-3787","authenticated-orcid":true,"given":"J. I.","family":"Gamez-Nava","sequence":"additional","affiliation":[{"name":"Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, JAL, Mexico"},{"name":"Unidad de Investigaci\u00f3n en Epidemiolog\u00eda Cl\u00ednica, Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Hospital de Especialidades, 44340 Guadalajara, JAL, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. M.","family":"Salda\u00f1a-Cruz","sequence":"additional","affiliation":[{"name":"Centro Universitario de Investigaciones Biom\u00e9dicas (CUIB), Universidad de Colima, 28040 Colima, COL, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. D.","family":"Murillo-Vazquez","sequence":"additional","affiliation":[{"name":"Doctorado en Farmacolog\u00eda, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (U de G), 44340 Guadalajara, JAL, Mexico"},{"name":"Unidad de Investigaci\u00f3n en Epidemiolog\u00eda Cl\u00ednica, Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Hospital de Especialidades, 44340 Guadalajara, JAL, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. L.","family":"Vazquez-Villegas","sequence":"additional","affiliation":[{"name":"Departamento de Epidemiolog\u00eda, Unidad M\u00e9dica Familiar 4, IMSS, 44220 Guadalajara, JAL, Mexico"},{"name":"Departamento de Salud P\u00fablica, CUCS, U de G, 44340 Guadalajara, JAL, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6572-3507","authenticated-orcid":true,"given":"S. A.","family":"Zavaleta-Mu\u00f1iz","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Posgrado, Facultad de Ciencias de la Salud, Universidad Ju\u00e1rez del Estado de Durango, 35050 G\u00f3mez Palacio, DGO, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6756-4316","authenticated-orcid":true,"given":"B. 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