1. The -174G/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis.
- Author
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Ruiz-Padilla AJ, Gamez-Nava JI, Saldaña-Cruz AM, Murillo-Vazquez JD, Vazquez-Villegas ML, Zavaleta-Muñiz SA, Martín-Márquez BT, Ponce-Guarneros JM, Rodriguez Jimenez NA, Flores-Chavez A, Sandoval-Garcia F, Vasquez-Jimenez JC, Cardona-Muñoz EG, Totsuka-Sutto SE, and Gonzalez-Lopez L
- Subjects
- Aged, Arthritis, Rheumatoid genetics, Arthritis, Rheumatoid pathology, Biomarkers, Pharmacological blood, Female, Genetic Markers, Genotype, Humans, Interleukin-6 blood, Isoxazoles adverse effects, Leflunomide, Male, Methotrexate adverse effects, Middle Aged, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Arthritis, Rheumatoid drug therapy, Interleukin-6 genetics, Isoxazoles administration & dosage, Methotrexate administration & dosage
- Abstract
Objective . To evaluate the association of -174G/C IL-6 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 IL-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 that IL-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., Competing Interests: The authors declare that they have no competing interests.
- Published
- 2016
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