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Influence of Promoter Polymorphisms of the Tnf-α (-308g/A) and IL-6 (-174g/C) Genes on Therapeutic Response to Etanercept in Rheumatoid Arthritis

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Authors
Jančić, Ivan
Sefik-Bukilica, Mirjana
Živojinović, Slađana
Damjanov, Nemanja
Spasovski, Vesna
Kotur, Nikola
Klaassen, Kristel
Pavlović, Sonja
Bufan, Biljana
Arsenović-Ranin, Nevena
Article (Published version)
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Abstract
Background: The study was undertaken to assess the influence of functional -308G/A TNF-alpha (rs 1800629) and -174G/C IL-6 (rs1800795) promoter polymorphisms on the therapeutic response to etanercept, a TNF-alpha. blocker, in patients with rheumatoid arthritis (RA). Methods: 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-alpha and -174G/C IL-6 polymorphisms by the PCR-RFLP method, and the influence of genotype on etanercept response was assessed. Results: No difference in the percentage of responders (patients who had DAS28 improvement > 1.2) between patients with the TNF-alpha -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 genot...ype 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/INF-alpha genotypes showed that patients with the IL-6 -174GG / TNF-alpha -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-alpha -308GG genotype were responders after 12 months of etanercept treatment. Conclusions: The study suggests that patients who are genetically low TNF-alpha and IL-6 producers are the best responders to etanercept therapy.

Source:
Journal of Medical Biochemistry, 2015, 34, 4, 414-421
Publisher:
  • Društvo medicinskih biohemičara Srbije, Beograd i Versita
Funding / projects:
  • Immune system plasticity during aging: Immunomodulatory capacity of oestrogens (RS-175050)

DOI: 10.2478/jomb-2014-0060

ISSN: 1452-8258

PubMed: 28356850

WoS: 000363003400004

Scopus: 2-s2.0-84942865195
[ Google Scholar ]
15
7
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/2331
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Jančić, Ivan
AU  - Sefik-Bukilica, Mirjana
AU  - Živojinović, Slađana
AU  - Damjanov, Nemanja
AU  - Spasovski, Vesna
AU  - Kotur, Nikola
AU  - Klaassen, Kristel
AU  - Pavlović, Sonja
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2331
AB  - Background: The study was undertaken to assess the influence of functional -308G/A TNF-alpha (rs 1800629) and -174G/C IL-6 (rs1800795) promoter polymorphisms on the therapeutic response to etanercept, a TNF-alpha. blocker, in patients with rheumatoid arthritis (RA). Methods: 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-alpha and -174G/C IL-6 polymorphisms by the PCR-RFLP method, and the influence of genotype on etanercept response was assessed. Results: No difference in the percentage of responders (patients who had DAS28 improvement > 1.2) between patients with the TNF-alpha -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/INF-alpha genotypes showed that patients with the IL-6 -174GG / TNF-alpha -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-alpha -308GG genotype were responders after 12 months of etanercept treatment. Conclusions: The study suggests that patients who are genetically low TNF-alpha and IL-6 producers are the best responders to etanercept therapy.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Influence of Promoter Polymorphisms of the Tnf-α (-308g/A) and IL-6 (-174g/C) Genes on Therapeutic Response to Etanercept in Rheumatoid Arthritis
VL  - 34
IS  - 4
SP  - 414
EP  - 421
DO  - 10.2478/jomb-2014-0060
ER  - 
@article{
author = "Jančić, Ivan and Sefik-Bukilica, Mirjana and Živojinović, Slađana and Damjanov, Nemanja and Spasovski, Vesna and Kotur, Nikola and Klaassen, Kristel and Pavlović, Sonja and Bufan, Biljana and Arsenović-Ranin, Nevena",
year = "2015",
abstract = "Background: The study was undertaken to assess the influence of functional -308G/A TNF-alpha (rs 1800629) and -174G/C IL-6 (rs1800795) promoter polymorphisms on the therapeutic response to etanercept, a TNF-alpha. blocker, in patients with rheumatoid arthritis (RA). Methods: 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-alpha and -174G/C IL-6 polymorphisms by the PCR-RFLP method, and the influence of genotype on etanercept response was assessed. Results: No difference in the percentage of responders (patients who had DAS28 improvement > 1.2) between patients with the TNF-alpha -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/INF-alpha genotypes showed that patients with the IL-6 -174GG / TNF-alpha -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-alpha -308GG genotype were responders after 12 months of etanercept treatment. Conclusions: The study suggests that patients who are genetically low TNF-alpha and IL-6 producers are the best responders to etanercept therapy.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Influence of Promoter Polymorphisms of the Tnf-α (-308g/A) and IL-6 (-174g/C) Genes on Therapeutic Response to Etanercept in Rheumatoid Arthritis",
volume = "34",
number = "4",
pages = "414-421",
doi = "10.2478/jomb-2014-0060"
}
Jančić, I., Sefik-Bukilica, M., Živojinović, S., Damjanov, N., Spasovski, V., Kotur, N., Klaassen, K., Pavlović, S., Bufan, B.,& Arsenović-Ranin, N.. (2015). Influence of Promoter Polymorphisms of the Tnf-α (-308g/A) and IL-6 (-174g/C) Genes on Therapeutic Response to Etanercept in Rheumatoid Arthritis. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 34(4), 414-421.
https://doi.org/10.2478/jomb-2014-0060
Jančić I, Sefik-Bukilica M, Živojinović S, Damjanov N, Spasovski V, Kotur N, Klaassen K, Pavlović S, Bufan B, Arsenović-Ranin N. Influence of Promoter Polymorphisms of the Tnf-α (-308g/A) and IL-6 (-174g/C) Genes on Therapeutic Response to Etanercept in Rheumatoid Arthritis. in Journal of Medical Biochemistry. 2015;34(4):414-421.
doi:10.2478/jomb-2014-0060 .
Jančić, Ivan, Sefik-Bukilica, Mirjana, Živojinović, Slađana, Damjanov, Nemanja, Spasovski, Vesna, Kotur, Nikola, Klaassen, Kristel, Pavlović, Sonja, Bufan, Biljana, Arsenović-Ranin, Nevena, "Influence of Promoter Polymorphisms of the Tnf-α (-308g/A) and IL-6 (-174g/C) Genes on Therapeutic Response to Etanercept in Rheumatoid Arthritis" in Journal of Medical Biochemistry, 34, no. 4 (2015):414-421,
https://doi.org/10.2478/jomb-2014-0060 . .

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