Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept

PloS One
A Ferreiro-IglesiasAntonio Gonzalez

Abstract

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651...Continue Reading

References

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Mar 29, 2014·Pharmacogenetics and Genomics·Ariana MontesAntonio Gonzalez
Jun 5, 2014·Journal of Clinical Pharmacology·Emma BoströmUlrika Wählby-Hamrén
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Apr 22, 2015·The Pharmacogenomics Journal·A Ferreiro-IglesiasA Gonzalez
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Jun 15, 2017·Lancet·Gerd R Burmester, Janet E Pope

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Citations

Jun 13, 2019·Journal of Clinical Medicine·Marialbert Acosta-HerreraJavier Martín
Jul 16, 2020·International Journal of Molecular Sciences·Dmitry S MikhaylenkoAndrey A Zamyatnin
Feb 25, 2021·Expert Review of Clinical Immunology·Ikram MezghicheElisabetta Bianchi
Jun 2, 2021·Auto- Immunity Highlights·Yolima Puentes-OsorioDaniel Taborda
Aug 2, 2021·Inflammation and Regeneration·Mineto Ota, Keishi Fujio

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Methods Mentioned

BETA
PCR
genotyping

Software Mentioned

Power
Statistica
BRAGGSS
R metafor package

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