Pathway analysis to identify genetic variants associated with efficacy of adalimumab in rheumatoid arthritis-Reference-Cited by-同舟云学术

Pathway analysis to identify genetic variants associated with efficacy of adalimumab in rheumatoid arthritis

Published:2017-07 Issue:10 Volume:18 Page:945-953
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Eektimmerman Frank¹,Swen Jesse J¹,Böhringer Stefan²,Huizinga Tom WJ³,Kooloos Wouter M¹,Allaart Cornelia F³,Guchelaar Henk-Jan¹

Affiliation:

1. Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands

2. Department of Medical Statistics & Bio-Informatics, Leiden University Medical Center, Leiden, The Netherlands

3. Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands

Abstract

Aim: About 30% of rheumatoid arthritis patients have no clinical benefit from TNF inhibitors. Genome-wide association (GWA) and candidate gene studies tested several putative genetic variants for TNF inhibitor efficacy with inconclusive results. Therefore, this study applied a systematic pathway analysis. Patients & methods: A total of 325 rheumatoid arthritis patients treated with adalimumab were genotyped for 223 SNPs. We tested the association between SNPs and European League Against Rheumatism response and remission at 14 weeks under the additive genetic model using logistic regression. Results: A total of 3 SNPs located in CD40LG (rs1126535), TANK (rs1267067) and VEGFA (rs25648) showed association with both end points. TNFAIP3 (rs2230926) had the strongest effect related to European League Against Rheumatism response. Conclusion: This exploratory study suggests that TNFAIP3, CD40LG, TANK and VEGFA play a role in the response to adalimumab treatment.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs-2017-0047

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