Investigation of genetically regulated gene expression and response to treatment in rheumatoid arthritis highlights an association between IL18RAP expression and treatment response.
Investigation of genetically regulated gene expression and response to treatment in rheumatoid arthritis highlights an association between IL18RAP expression and treatment response.
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DOI：
10.1136/annrheumdis-2020-217204
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发表时间：
2020-11
影响因子：
27.4
通讯作者：
Cordell HJ
中科院分区：
文献类型：
--
作者：
Cherlin S;Lewis MJ;Plant D;Nair N;Goldmann K;Tzanis E;Barnes MR;McKeigue P;Barrett JH;Pitzalis C;Barton A;MATURA Consortium;Cordell HJ
在这项研究中，我们试图调查3158名患有类风湿性关节炎的欧洲祖先患者的基因调控基因表达(使用各种参考小组预测的)和抗肿瘤坏死因子(抗肿瘤坏死因子)治疗反应(血沉(ESR)的变化)之间是否存在任何关联。使用PrediXcan软件包和三个不同的参考小组，在3158名受试者的全部队列中(以及在由1575名英国患者组成的子队列中)估计了基因表达的受基因调控的部分。对估计的表达与抗肿瘤坏死因子治疗反应的相关性进行测试。作为一项复制/验证实验，我们还使用一个独立的复制数据集，研究了血沉变化与全血和滑膜组织中白细胞介素18受体辅助蛋白(IL18RAP)基因表达的测量之间的相关性，该数据集使用了直接测量(通过RNA测序)基因表达的常规合成疾病修改药物的患者。我们发现，IL18RAP的预测表达在所有参照板上显示出与治疗反应相关的一致信号。在我们独立的复制数据集中，IL18RAP在全血中的表达与血沉在基线和随访期间的变化呈正相关(r=−0.35，p=0.0091)。血沉变化与滑膜组织中IL18RAP的表达呈正相关(r=−0.28，p=0.02)。我们的结果表明，IL18RAP的表达作为类风湿关节炎治疗反应的潜在预测因子值得进一步研究，因为类风湿关节炎对特定药物类型没有特异性。
In this study, we sought to investigate whether there was any association between genetically regulated gene expression (as predicted using various reference panels) and anti-tumour necrosis factor (anti-TNF) treatment response (change in erythrocyte sedimentation rate (ESR)) using 3158 European ancestry patients with rheumatoid arthritis. The genetically regulated portion of gene expression was estimated in the full cohort of 3158 subjects (as well as within a subcohort consisting of 1575 UK patients) using the PrediXcan software package with three different reference panels. Estimated expression was tested for association with anti-TNF treatment response. As a replication/validation experiment, we also investigated the correlation between change in ESR with measured gene expression at the Interleukin 18 Receptor Accessory Protein (IL18RAP) gene in whole blood and synovial tissue, using an independent replication data set of patients receiving conventional synthetic disease modifying anti-rheumatic drugs, with directly measured (via RNA sequencing) gene expression. We found that predicted expression of IL18RAP showed a consistent signal of association with treatment response across the reference panels. In our independent replication data set, IL18RAP expression in whole blood showed correlation with the change in ESR between baseline and follow-up (r=−0.35, p=0.0091). Change in ESR was also correlated with the expression of IL18RAP in synovial tissue (r=−0.28, p=0.02). Our results suggest that IL18RAP expression is worthy of further investigation as a potential predictor of treatment response in rheumatoid arthritis that is not specific to a particular drug type.
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影响因子：
5.5
作者：
Barrera, P;van der Maas, A;van Riel, PLCM
通讯作者：
van Riel, PLCM
影响因子：
7
作者：
Battle A;Mostafavi S;Zhu X;Potash JB;Weissman MM;McCormick C;Haudenschild CD;Beckman KB;Shi J;Mei R;Urban AE;Montgomery SB;Levinson DF;Koller D
通讯作者：
Koller D
影响因子：
2.1
作者：
Cherlin S;Plant D;Taylor JC;Colombo M;Spiliopoulou A;Tzanis E;Morgan AW;Barnes MR;McKeigue P;Barrett JH;Pitzalis C;Barton A;Consortium M;Cordell HJ
通讯作者：
Cordell HJ
影响因子：
5.5
作者：
Hyrich, K. L.;Watson, K. D.;Symmons, D. P. M.
通讯作者：
Symmons, D. P. M.
影响因子：
--
作者：
Joosten, LAB;Radstake, TRD;van den Berg, WB
通讯作者：
van den Berg, WB