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.
abstract: Objective. To evaluate the association of -174G/CIL-6polymorphism 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 forIL-6-174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2).Results. Patients with MTX or LEF had significant decrement in DAS-28 (p< 0.001); nevertheless, only 14% and 12.5% achieved DAS-28 < 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: 1.07-1.56). 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 = 1.05-2.3;p= 0.003), or CC (RR = 1.83; 95% CI = 1.07-3.14;p= 0.001). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03-1.72;p= 0.02). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded thatIL-6-174G/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.
authors.affiliation: Departamento de Medicina Interna-Reumatología, Hospital General Regional 110, IMSS, 44710 Guadalajara, JAL, Mexico; Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (U de G), 44340 Guadalajara, JAL, Mexico.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ruiz-Padilla
authors.affiliation: Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, JAL, Mexico; Unidad de Investigación en Epidemiología Clínica, Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Hospital de Especialidades, 44340 Guadalajara, JAL, Mexico.
authors.forename: J I
authors.identifier: 0000-0003-0001-3787
authors.initials: JI
authors.lastname: Gamez-Nava
authors.affiliation: Centro Universitario de Investigaciones Biomédicas (CUIB), Universidad de Colima, 28040 Colima, COL, Mexico.
authors.forename: A M
authors.initials: AM
authors.lastname: Saldaña-Cruz
authors.affiliation: Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (U de G), 44340 Guadalajara, JAL, Mexico; Unidad de Investigación en Epidemiología Clínica, Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Hospital de Especialidades, 44340 Guadalajara, JAL, Mexico.
authors.forename: J D
authors.initials: JD
authors.lastname: Murillo-Vazquez
authors.affiliation: Departamento de Epidemiología, Unidad Médica Familiar 4, IMSS, 44220 Guadalajara, JAL, Mexico; Departamento de Salud Pública, CUCS, U de G, 44340 Guadalajara, JAL, Mexico.
authors.forename: M L
authors.initials: ML
authors.lastname: Vazquez-Villegas
authors.affiliation: División de Posgrado, Facultad de Ciencias de la Salud, Universidad Juárez del Estado de Durango, 35050 Gómez Palacio, DGO, Mexico.
authors.forename: S A
authors.identifier: 0000-0001-6572-3507
authors.initials: SA
authors.lastname: Zavaleta-Muñiz
authors.affiliation: Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético (IIRSME), CUCS, U de G, 44340 Guadalajara, JAL, Mexico.
authors.forename: B T
authors.identifier: 0000-0002-6756-4316
authors.initials: BT
authors.lastname: Martín-Márquez
authors.affiliation: Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (U de G), 44340 Guadalajara, JAL, Mexico; Unidad Médica Familiar 97, IMSS, 46470 Magdalena, JAL, Mexico.
authors.forename: J M
authors.initials: JM
authors.lastname: Ponce-Guarneros
authors.affiliation: Departamento de Medicina Interna-Reumatología, Hospital General Regional 110, IMSS, 44710 Guadalajara, JAL, Mexico; Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (U de G), 44340 Guadalajara, JAL, Mexico.
authors.forename: N A
authors.identifier: 0000-0001-7643-6298
authors.initials: NA
authors.lastname: Rodriguez Jimenez
authors.affiliation: Unidad de Investigación en Epidemiología Clínica, Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Hospital de Especialidades, 44340 Guadalajara, JAL, Mexico; Centro Universitario de Investigaciones Biomédicas (CUIB), Universidad de Colima, 28040 Colima, COL, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Flores-Chavez
authors.affiliation: Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético (IIRSME), CUCS, U de G, 44340 Guadalajara, JAL, Mexico.
authors.forename: F
authors.initials: F
authors.lastname: Sandoval-Garcia
authors.affiliation: Centro Universitario de Investigaciones Biomédicas (CUIB), Universidad de Colima, 28040 Colima, COL, Mexico.
authors.forename: J C
authors.initials: JC
authors.lastname: Vasquez-Jimenez
authors.affiliation: Departamento de Fisiología, CUCS, U de G, 44340 Guadalajara, JAL, Mexico.
authors.forename: E G
authors.identifier: 0000-0001-7868-667X
authors.initials: EG
authors.lastname: Cardona-Muñoz
authors.affiliation: Departamento de Fisiología, CUCS, U de G, 44340 Guadalajara, JAL, Mexico.
authors.forename: S E
authors.initials: SE
authors.lastname: Totsuka-Sutto
authors.affiliation: Departamento de Medicina Interna-Reumatología, Hospital General Regional 110, IMSS, 44710 Guadalajara, JAL, Mexico; Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, JAL, Mexico.
authors.forename: L
authors.identifier: 0000-0002-6517-6344
authors.initials: L
authors.lastname: Gonzalez-Lopez
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D054316:Biomarkers, Pharmacological / Q000097:blood; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007555:Isoxazoles / Q000008:administration & dosage* / Q000009:adverse effects; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D054316:Biomarkers, Pharmacological; D005819:Genetic Markers; D015850:Interleukin-6; D007555:Isoxazoles; D000077339:Leflunomide; D008727:Methotrexate