Stojanović Sonja, Jevtović-Stoimenov Tatjana, Stanković Aleksandra, Pavlović Dušica, Neković Jovan, Stamenković Bojana, Dimić Aleksandar, Marinković Milena
Srp Arh Celok Lek. 2011 Nov-Dec;139(11-12):784-9. doi: 10.2298/sarh1112784s.
Genetic markers are significant predictive factors in the assessment of therapeutic response of rheumatoid arthritis (RA) to biological medication.
The aim of the study was to determinate the association of TNF-alpha -308 G/A polymorphism with a high RA activity and its predictive value in therapeutic response after 12 months of treatment with Etanercept.
The study enrolled 132 patients with RA treated with Methotrexate (MTX) and 58 control subjects. The -308 TNF polymorphism was examined using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). The patients were divided into two groups: group A with A/A and A/G genotype and group G with G/G genotype. After 12 months, beside MTX, Etanercept was introduced in 36 patients. We compared clinical activity among the groups at the beginning and after one year of therapy by using DAS28 SE (Disease activity score with sedimentation).
There was no significant difference found in the distribution of G and A allele in the RA group compared to the control group. A significantly higher disease activity was noticed in A compared to the G group (DAS28 SE: 6.31 to 5.81; p < 0.05). The patients with A allele kept the majority of the disease activity even after a year of study (DAS28 SE: 5.25 to 3.89). After a year of MTX and Etanercept therapy, a significantly larger proportion of patients in the G group displayed a good clinical response to treatment compared to the A group (81.5% to 25%; p < 0.05). The average change of DAS28 SE in G group was 2.24, while in the A group DAS 28 reduction was significantly lower (1.17; p = 0.005).
There was no significant difference in the frequency of A in the patients with RA compared to healthy subjects. The presence of A allele is associated with more serious clinical presentation of the disease and lower therapeutic response to Etanercept.
基因标记是评估类风湿关节炎（RA）对生物药物治疗反应的重要预测因素。
本研究旨在确定肿瘤坏死因子-α（TNF-α）-308 G/A多态性与高RA活动度的关联及其在接受依那西普治疗12个月后治疗反应中的预测价值。
本研究纳入了132例接受甲氨蝶呤（MTX）治疗的RA患者和58例对照受试者。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测-308 TNF多态性。患者分为两组：A组为A/A和A/G基因型，G组为G/G基因型。12个月后，除MTX外，36例患者加用依那西普。我们使用DAS28 SE（血沉校正的疾病活动评分）比较了治疗开始时和治疗一年后两组间的临床活动度。
与对照组相比，RA组中G和A等位基因的分布无显著差异。与G组相比，A组的疾病活动度显著更高（DAS28 SE：6.31对5.81；p<0.05）。即使经过一年的研究，携带A等位基因的患者仍保持大部分疾病活动度（DAS28 SE：5.25对3.89）。经过一年的MTX和依那西普治疗，与A组相比，G组中对治疗有良好临床反应的患者比例显著更高（81.5%对25%；p<0.05）。G组DAS28 SE的平均变化为2.24，而A组DAS 28的降低显著更低（1.17；p = 0.005）。
与健康受试者相比，RA患者中A的频率无显著差异。A等位基因的存在与疾病更严重的临床表现以及对依那西普较低的治疗反应相关。
