AHR-dependent genes and response to MTX therapy in rheumatoid arthritis patients.
Adult
Aged
Aged, 80 and over
Alleles
Antirheumatic Agents
/ therapeutic use
Arthritis, Rheumatoid
/ drug therapy
Drug Resistance
/ genetics
Female
Genes
/ genetics
Genotyping Techniques
Humans
Male
Methotrexate
/ therapeutic use
Middle Aged
Polymorphism, Single Nucleotide
/ genetics
Receptors, Aryl Hydrocarbon
/ genetics
Reduced Folate Carrier Protein
/ genetics
Treatment Outcome
Young Adult
Journal
The pharmacogenomics journal
ISSN: 1473-1150
Titre abrégé: Pharmacogenomics J
Pays: United States
ID NLM: 101083949
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
14
10
2020
accepted:
23
04
2021
revised:
08
04
2021
pubmed:
25
7
2021
medline:
11
3
2022
entrez:
24
7
2021
Statut:
ppublish
Résumé
Methotrexate (MTX) is the first-line therapy for rheumatoid arthritis. Nevertheless, MTX resistance is quite a common issue in clinical practice. There are some premises that aryl hydrocarbon receptor (AhR) gene battery may take part in MTX metabolism. In the present retrospective study, we analyzed genes expression of AHR genes battery associated with MTX metabolism in whole blood of RA patients with good and poor response to MTX treatment. Additionally, sequencing, genotyping and bioinformatics analysis of AHR repressor gene (AHRR) c.565C > G (rs2292596) and c.1933G > C (rs34453673) have been performed. Theoretically, both changes may have an impact on H3K36me3 and H3K27me3. Evolutionary analysis revealed that rs2292596 may be possibly damaging. Allele G in rs2292596 and DAS28 seems to be associated with a higher risk of poor response to MTX treatment in RA. RA patients with poor response to MTX treatment revealed upregulated AhR and SLC19A1 mRNA level. Treatment with IL-6 inhibitor may be helpful to overcome the low-dose MTX resistance. Analysis of gene expression revealed possible another cause of poor response to MTX treatment which is different from that observed in the case of acute lymphoblastic leukemia.
Identifiants
pubmed: 34302046
doi: 10.1038/s41397-021-00238-4
pii: 10.1038/s41397-021-00238-4
pmc: PMC8455325
doi:
Substances chimiques
Antirheumatic Agents
0
Receptors, Aryl Hydrocarbon
0
Reduced Folate Carrier Protein
0
SLC19A1 protein, human
0
Methotrexate
YL5FZ2Y5U1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
608-621Informations de copyright
© 2021. The Author(s).
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