Cristina L Dávila-Fajardo1, Ana Márquez, Dora Pascual-Salcedo, Manuel J Moreno Ramos, Rosa García-Portales, César Magro, Juan J Alegre-Sancho, Alejandro Balsa, José Cabeza-Barrera, Enrique Raya, Javier Martín. 1. aInstituto de Parasitología y Biomedicina López-Neyra, CSIC bDepartment of Clinical Pharmacy, UGC Farmacia Granada cDepartment of Rheumatology, Instituto de Investigación Biosanitaria de Granada, San Cecilio University Hospital, Granada Departments of dImmunology eRheumatology, IdiPAZ, RIER, La Paz University Hospital, Madrid fDepartment of Rheumatology, Virgen de la Arrixaca University Hospital, Murcia gDepartment of Rheumatology, Virgen de la Victoria University Hospital, Málaga hDepartment of Rheumatology, Doctor Peset Hospital, Valencia, Spain.
Abstract
BACKGROUND: The 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 METHODS: Our 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. RESULTS: The -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). CONCLUSION: Our results support the role of the -174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.
BACKGROUND: The 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 METHODS: Our 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. RESULTS: The -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). CONCLUSION: Our results support the role of the -174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.
Authors: M Fabris; L Quartuccio; C Fabro; S Sacco; S Lombardi; R Ramonda; D Biasi; D Punzi; S Adami; I Olivieri; F Curcio; S De Vita Journal: Pharmacogenomics J Date: 2015-07-07 Impact factor: 3.550
Authors: Erika H Noss; Hung N Nguyen; Sook Kyung Chang; Gerald F M Watts; Michael B Brenner Journal: Proc Natl Acad Sci U S A Date: 2015-11-17 Impact factor: 11.205
Authors: A J Ruiz-Padilla; J I Gamez-Nava; A M Saldaña-Cruz; J D Murillo-Vazquez; M L Vazquez-Villegas; S A Zavaleta-Muñiz; B T Martín-Márquez; J M Ponce-Guarneros; N A Rodriguez Jimenez; A Flores-Chavez; F Sandoval-Garcia; J C Vasquez-Jimenez; E G Cardona-Muñoz; S E Totsuka-Sutto; L Gonzalez-Lopez Journal: Biomed Res Int Date: 2016-09-21 Impact factor: 3.411