Tumour necrosis factor (TNF)α-308 G/G promoter polymorphism and TNFα levels correlate with a better response to adalimumab in patients with rheumatoid arthritis
Tumour necrosis factor (TNF)α-308 G/G promoter polymorphism and TNFα levels correlate with a better response to adalimumab in patients with rheumatoid arthritis
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DOI：
10.1080/03009740600904284
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发表时间：
2006-01-01
影响因子：
2.1
通讯作者：
Valenzuela, O.
中科院分区：
文献类型：
--
作者：
Cuchacovich, M.;Soto, L.;Valenzuela, O.
目的：探讨类风湿关节炎(RA)患者肿瘤坏死因子-308(TNF-α)基因启动子区-308位基因多态性和循环中肿瘤坏死因子-α水平对阿达单抗治疗疗效的影响。方法：采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对81例活动期类风湿关节炎(RA)患者进行-308位基因分型，并将其分为G/A和G/G两组。所有患者每隔一周皮下注射40毫克阿达利马。我们使用28个关节的疾病活动性评分(DAS28)比较了8、16和24周时两组患者对阿达利单抗的临床反应。结果：两组患者均较基线有显著改善。24周时，两组间差异有统计学意义。我们发现88.2%的G/G和68.4%的G/A是DAS28应答者(p=0.05)。24周时，G/G组和G/A组的-308多态得分分别提高了2.5+/-1.3和1.8+/-1.3(p=0.04)。G/A组血清肿瘤坏死因子-α水平中位数低于G/G组，第8周和第24周差异有统计学意义(P<；0.039和P<；0.043)。当比较基线水平与整个组在8周、16周和24周时达到的水平时，只有有反应的患者随着时间的推移显示出总体上有统计学意义的肿瘤坏死因子α升高(p<；0.000001)。结论：在接受阿达单抗治疗的智利类风湿关节炎患者中，发现DAS28改善、-308G/G多态和循环中肿瘤坏死因子α水平升高之间的关系。
Objective: To investigate the influence of -308 tumour necrosis factor-alpha (TNF alpha) promoter polymorphism and circulating TNF alpha levels in the clinical response to adalimumab treatment in patients with rheumatoid arthritis (RA).Methods: Eighty-one patients with active RA were genotyped for the -308 TNF alpha polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and subdivided into two groups for each polymorphism (G/A and G/G genotype). All received 40 mg of adalimumab subcutaneously every other week. We compared the groups' clinical responses to adalimumab at 8, 16, and 24 weeks using the Disease Activity Score in 28 joints (DAS28).Results: Both groups showed a significant improvement from baseline. A significant difference between groups was found at week 24. We found that 88.2% of G/G versus 68.4% of G/A for the -308 polymorphism were DAS28 responders (p=0.05). The score improvement at week 24 was 2.5 +/- 1.3 in the G/G group and 1.8 +/- 1.3 in the G/A group for the -308 polymorphism (p=0.04). The median of serum TNF alpha levels of the G/A group were lower than those of the G/G group, and statistically different at weeks 8 and 24 (p < 0.039 and p < 0.043). When comparing baseline levels to those achieved at 8, 16, and 24 weeks for the whole group, only responder patients showed a statistically significant overall increase in TNF alpha over time (p < 0.000001).Conclusion: A relationship between DAS28 improvement, the -308 G/G polymorphism, and increased circulating TNF alpha levels was found in Chilean RA patients treated with adalimumab.