A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizumab in rheumatoid arthritis patients View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-01-16

AUTHORS

Cécile Luxembourger, Adeline Ruyssen-Witrand, Chayma Ladhari, Cécile Rittore, Yannick Degboe, Jean-Francis Maillefert, Philippe Gaudin, Hubert Marotte, Daniel Wendling, Christian Jorgensen, Alain Cantagrel, Arnaud Constantin, Delphine Nigon, Isabelle Touitou, Jacques-Eric Gottenberg, Yves-Marie Pers

ABSTRACT

Biological disease-modifying anti-rheumatic drugs (bDMARDs) have changed care of patients with rheumatoid arthritis (RA). However, bDMARDs are costly, can lead to serious infections, and induce a sustained remission in only 30% of RA patients. In this study, we sought to determine if the clinical response to treatment with Tocilizumab (TCZ), an IL-6 inhibitor, varied with genetic background. The efficacy of TCZ was assessed using the European League Against Rheumatism (EULAR) response criteria, measured after 3 months of treatment in two samples of French RA patients (TOCI and ROC studies). Single nucleotide polymorphisms (SNPs) in 21 candidate genes were genotyped using KasPar method (LGC-genomics, UK) and then analyzed to determine their contribution to variation in the response to treatment. One hundred twenty-three patients in the TOCI group (79.8%) and 48 patients in the ROC group (80%) experienced good or moderate EULAR response. The clinical response to treatment was associated with SNP genotype in the gene IL6R, with patients with the homozygous AA-genotype for rs12083537 (IL6R) showing a significantly better response than homozygous or heterozygous patients with the G allele [TOCI: 87.5% of responders for AA genotype vs. 72.2% for AG or GG genotype (p = 0.018); ROC patients: 89.2% of responders for AA genotype vs. 65.2% for AG or GG genotype, p = 0.044]. A meta-analysis combining data from the two cohorts confirmed the lower response rate in patients carrying a copy of the G allele (OR (95% CI) = 0.35 (0.16-0.61), p = 0.001). No association was found with any of the other SNPs tested. More... »

PAGES

1-7

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URI

http://scigraph.springernature.com/pub.10.1038/s41397-019-0072-6

DOI

http://dx.doi.org/10.1038/s41397-019-0072-6

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https://app.dimensions.ai/details/publication/pub.1111411295

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30647443


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

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curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41397-019-0072-6'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41397-019-0072-6'

Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41397-019-0072-6'


 

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