Jančić Ivan, Šefik-Bukilica Mirjana, Živojinović Slađana, Damjanov Nemanja, Spasovski Vesna, Kotur Nikola, Klaassen Kristel, Pavlović Sonja, Bufan Biljana, Arsenović-Ranin Nevena
Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
J Med Biochem. 2015 Oct;34(4):414-421. doi: 10.2478/jomb-2014-0060. Epub 2015 Sep 19.
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 improvement > 1.2) 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.
本研究旨在评估功能性-308G/A肿瘤坏死因子-α（TNF-α，rs 1800629）和-174G/C白细胞介素-6（IL-6，rs1800795）启动子多态性对类风湿关节炎（RA）患者使用TNF-α阻滞剂依那西普治疗反应的影响。
对73例活动性RA患者进行研究，在基线期以及治疗后6个月和12个月进行观察。根据欧洲抗风湿病联盟反应标准评估治疗反应。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对患者的-308G/A TNF-α和-174G/C IL-6多态性进行基因分型，并评估基因型对依那西普反应的影响。
治疗6个月和12个月后，TNF-α -308GG、GA和AA基因型患者之间的反应者（疾病活动评分28改善>1.2的患者）百分比无差异。治疗12个月后，与GC或CC基因型患者相比，IL-6 -174GG基因型患者的反应者百分比显著增加（卡方检验，p = 0.006）。根据患者的IL-6/TNF-α联合基因型进行评估显示，与其他联合基因型患者相比，反应者中IL-6 -174GG / TNF-α-308GG基因型患者更为常见（卡方检验，p = 0.022）。更确切地说，所有IL-6 -174GG / TNF-α-308GG联合基因型患者在依那西普治疗12个月后均为反应者。
该研究表明，TNF-α和IL-6基因产生水平较低的患者是依那西普治疗的最佳反应者。
