Influence of Promoter Polymorphisms of the Tnf-α (-308g/A) and IL-6 (-174g/C) Genes on Therapeutic Response to Etanercept in Rheumatoid Arthritis
| Autor: | Ivan Jančić, Nevena Arsenović-Ranin, Nemanja Damjanov, Biljana Bufan, Sonja Pavlovic, M. Sefik-Bukilica, Vesna Spasovski, Kristel Klaassen, Nikola Kotur, Slađana Živojinović |
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| Rok vydání: | 2015 |
| Předmět: |
musculoskeletal diseases
rheumatoid arthritis 174G/C IL-6 gene polymorphism medicine.medical_specialty Gastroenterology 174g/c il-6 gene polymorphism Etanercept lcsh:Biochemistry 308G/A TNF-α genski polimorfizam 03 medical and health sciences 0302 clinical medicine Internal medicine Genotype medicine Chi-square test 174G/C IL-6 genski polimorfizam lcsh:QD415-436 skin and connective tissue diseases Interleukin 6 reumatoidni artritis 030304 developmental biology pharmacogenetics 308G/A TNF-α gene polymorphism 030203 arthritis & rheumatology 0303 health sciences Original Paper biology business.industry farmakogenomika medicine.disease 3. Good health Rheumatoid arthritis 308g/a tnf-α gene polymorphism biology.protein Tumor necrosis factor alpha business etanercept Pharmacogenetics Rheumatism medicine.drug |
| Zdroj: | Journal of Medical Biochemistry Journal of Medical Biochemistry, Vol 34, Iss 4, Pp 414-421 (2015) Journal of Medical Biochemistry (2015) 34(4):414-421 |
| ISSN: | 1452-8258 |
| Popis: | The study was undertaken to assess the influence of functional -308G/A TNF-α (rs 1800629) and -174G/C IL-6 (rs1800795) promoter polymorphisms on the therapeutic response to etanercept, a TNF-α blocker, in patients with rheumatoid arthritis (RA).Seventy-three patients suffering from active RA were studied, at baseline and 6 and 12 months after therapy. The therapeutic response was estimated according to the European League Against Rheumatism response criteria. Patients were genotyped for -308G/A TNF-α and -174G/C IL-6 polymorphisms by the PCR-RFLP method, and the influence of genotype on etanercept response was assessed.No difference in the percentage of responders (patients who had DAS28 improvement1.2) between patients with the TNF-α-308GG and GA and AA genotype was detected after 6 and 12 months of treatment. After 12 months of treatment the percentage of responders was significantly increased in patients with the IL-6 -174GG genotype compared with those with the GC or CC genotype (p=0.006 by Chi-square test). Evaluation of the patients according to their combined IL-6/TNF-α genotypes showed that patients with the IL-6 -174GG / TNF-α-308GG genotype were more frequent among the responders compared to those with other combined genotypes (p=0.022 by Chi-square test). More precisely, all patients with the combined IL-6 -174GG / TNF-α-308GG genotype were responders after 12 months of etanercept treatment.The study suggests that patients who are genetically low TNF-α and IL-6 producers are the best responders to etanercept therapy.Genetički faktori su značajni za predviđanje ishoda lečenja bolesnika sa reumatoidnim artritisom (RA). Cilj studije bio je da se ispita uticaj -308G/A TNF-α (rs 1800629) i -174G/C IL-6 (rs1800795) promotorskih polimorfizama na terapijski odgovor na etanercept.U studiju su bila uključena 73 pacijenta sa aktivnim RA. Terapijski odgovor je procenjivan posle 6 i 12 meseci terapije po kriterijumima Evropske lige protiv reumatizma. Genotipizacija pacijenata za polimorfizme -308G/A TNF-α i -174G/C IL-6 urađena je PCR-RFLP metodom i procenjivan je uticaj genotipova na odgovor na etanercept.Nije bilo razlike u procentu respondera (pacijenti kod kojih se DAS28 popravio1,2) između pacijenata sa TNF-α-308GG, GA i AA genotipom ni posle 6 ni posle 12 meseci tretmana. Posle 12 meseci lečenja procenat respondera je bio značajno veći kod pacijenata sa IL-6 -174GG u odnosu na pacijente sa GC ili CC genotipom (p=0,006, χStudija pokazuje da bolesnici sa genotipovima koji se povezuju sa manjom produkcijom TNF-α i IL-6 najbolje odgovaraju na terapiju etanerceptom. |
| Databáze: | OpenAIRE |
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