School of Medicine, University of Manchester, Manchester, M13 9PT, UK.
NIHR Manchester Biomedical Research Center, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Center, Manchester, M13 9WL, UK.
Pharmacogenomics. 2020 Nov;21(16):1151-1156. doi: 10.2217/pgs-2020-0043. Epub 2020 Oct 30.
TNF inhibitor drugs are a treatment option for rheumatoid arthritis, but response is not universal. Response is typically measured using the composite 4-component (4C) disease activity score 28 (DAS28) which contains more subjective measures. This study used a validated 2-component (2C) DAS28 score to determine whether SNPs associated with response were replicated in the UK population. A literature review identified TNF inhibitor response SNPs. Linear regression was conducted to replicate associations with 4C or 2C-DAS28 response. Eighteen independent SNPs were analyzed in 1828 patients. One and four associations with 4C and 2C-DAS28 response respectively were identified (p ≤ 0.05). Further genetic associations were replicated using the 2C-DAS28 which may reflect the objective nature of 2C-AS28.
TNF 抑制剂药物是类风湿关节炎的一种治疗选择,但并非对所有人都有效。通常使用包含更多主观指标的复合 4 成分(4C)疾病活动评分 28(DAS28)来衡量反应。本研究使用经过验证的 2 成分(2C)DAS28 评分来确定与反应相关的单核苷酸多态性是否在英国人群中得到复制。通过文献回顾确定了 TNF 抑制剂反应 SNP。进行线性回归以复制与 4C 或 2C-DAS28 反应的关联。在 1828 名患者中分析了 18 个独立的 SNP。分别在 4C 和 2C-DAS28 反应中鉴定出 1 个和 4 个关联(p ≤ 0.05)。使用 2C-DAS28 进一步复制了遗传关联,这可能反映了 2C-AS28 的客观性质。