Confirmation of −174G/C interleukin-6 gene promoter polymorphism as a genetic marker predicting antitumor necrosis factor treatment outcome

• Published in: Pharmacogenetics and genomics Vol. 24; no. 1; pp. 1 - 5
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health | Lippincott Williams & Wilkins 01-01-2014
• 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
• ISSN: 1744-6872; 1744-6880
• DOI: 10.1097/FPC.0000000000000013

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.