Laboratorio Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Travesia Choupana sn, Santiago de Compostela, 15706, Spain.
Arthritis Res Ther. 2010;12(2):R72. doi: 10.1186/ar2990. Epub 2010 Apr 27.
We aimed to replicate the strong associations that a recent genome wide association study (GWAS) has found between 16 single nucleotide polymorphisms (SNPs) and response to anti-tumour necrosis factor (TNF) treatment in 89 patients with rheumatoid arthritis (RA). This study is very important because, according to published simulations, associations as strong as the reported ones will mean that these SNPs could be used as predictors of response at the individual level.
Disease activity score (DAS28) was evaluated in 151 anti-TNF treated patients with RA of Spanish ancestry at baseline and every 3 months thereafter. Genotypes of the 16 putative predictor SNPs were obtained by single-base extension. Association between the relative change in DAS28 and SNP genotypes was tested by linear regression. In addition, logistic regression was applied to compare genotypes in non-responders (n = 34) versus good-responders (n = 61) following the EULAR response criteria.
None of the analyses showed any significant association between the 16 SNPs and response to anti-TNF treatments at 3 or 6 months. Results were also negative when only patients treated with infliximab (66.9% of the total) were separately analyzed. These negative results were obtained in spite of a very good statistical power to replicate the reported strong associations.
We still do not have any sound evidence of genetic variants associated with RA response to anti-TNF treatments. In addition, the possibility we had envisaged of using the results of a recent GWAS for prediction in individual patients should be dismissed.
我们旨在复制最近全基因组关联研究（GWAS）在 89 例类风湿关节炎（RA）患者中发现的 16 个单核苷酸多态性（SNP）与抗肿瘤坏死因子（TNF）治疗反应之间的强关联。这项研究非常重要，因为根据已发表的模拟研究，报告的关联强度如此之大，意味着这些 SNP 可以作为个体水平反应的预测因子。
在 151 名西班牙裔抗 TNF 治疗的 RA 患者中，在基线时和此后每 3 个月评估疾病活动评分（DAS28）。通过单碱基延伸获得 16 个假定预测 SNP 的基因型。通过线性回归测试 DAS28 的相对变化与 SNP 基因型之间的关联。此外，应用逻辑回归比较根据 EULAR 反应标准的无应答者（n = 34）与良好应答者（n = 61）的基因型。
在 3 个月或 6 个月时，16 个 SNP 与抗 TNF 治疗反应之间的任何分析均未显示出任何显著关联。当仅分析接受英夫利昔单抗治疗的患者（占总数的 66.9%）时，结果仍然为阴性。尽管有很强的统计能力来复制报告的强关联，但仍未获得阴性结果。
我们仍然没有任何与 RA 对 TNF 治疗反应相关的遗传变异的可靠证据。此外，我们曾设想过利用最近的 GWAS 结果进行个体患者的预测，这种可能性应该被否定。
