PT  - JOURNAL ARTICLE
AU  - Cherlin, Svetlana
AU  - Lewis, Myles J
AU  - Plant, Darren
AU  - Nair, Nisha
AU  - Goldmann, Katriona
AU  - Tzanis, Evan
AU  - Barnes, Michael R
AU  - McKeigue, Paul
AU  - Barrett, Jennifer H
AU  - Pitzalis, Costantino
AU  - Barton, Anne
AU - MATURA Consortium
AU  - Cordell, Heather J
TI  - Investigation of genetically regulated gene expression and response to treatment in rheumatoid arthritis highlights an association between <em>IL18RAP</em> expression and treatment response
AID  - 10.1136/annrheumdis-2020-217204
DP  - 2020 Nov 01
TA  - Annals of the Rheumatic Diseases
PG  - 1446--1452
VI  - 79
IP  - 11
4099  - http://ard.bmj.com/content/79/11/1446.short
4100  - http://ard.bmj.com/content/79/11/1446.full
SO  - Ann Rheum Dis2020 Nov 01; 79
AB  - Objectives 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.Methods 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.Results 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).Conclusion 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.