Next Article in Journal
Validation of the Italian Version of the Educational Needs Assessment Tool in Rheumatoid Arthritis Patients and Factors Associated with Educational Needs
Next Article in Special Issue
Comparison of Serum Pharmacodynamic Biomarkers in Prednisone-Versus Deflazacort-Treated Duchenne Muscular Dystrophy Boys
Previous Article in Journal
Personalized Medicine for Antibiotics: The Role of Nanobiosensors in Therapeutic Drug Monitoring
Previous Article in Special Issue
Advances in Genetic Characterization and Genotype–Phenotype Correlation of Duchenne and Becker Muscular Dystrophy in the Personalized Medicine Era
Open AccessArticle

Clinical and Laboratory Associations with Methotrexate Metabolism Gene Polymorphisms in Rheumatoid Arthritis

1
Northern Ireland Centre for Stratified Medicine (NICSM), Biomedical Sciences Research Institute, Ulster University, C-TRIC Building, Londonderry BT47 6SB, UK
2
Respiratory Medicine Department and Clinical Trials Unit, Queen Alexandra Hospital, Portsmouth PO6 3LY, UK
3
Rheumatology Department, Western Health and Social Care Trust, Londonderry BT47 6SB, UK
4
Cardiac Assessment Unit, Western Health and Social Care Trust, Omagh BT79 0NR, UK
5
Mass Spectrometry Centre, Biomedical Sciences Research Institute (BMSRI), School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, UK
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2020, 10(4), 149; https://doi.org/10.3390/jpm10040149
Received: 20 August 2020 / Revised: 21 September 2020 / Accepted: 24 September 2020 / Published: 26 September 2020
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of disease-modifying anti-rheumatic drugs (DMARDs) can influence treatment efficacy and toxicity. This study explored the relationship between DMARD-metabolising gene variants and plasma metabolite levels in RA patients. DMARD metabolite concentrations were determined by tandem mass-spectrometry in plasma samples from 100 RA patients with actively flaring disease collected at two intervals. Taqman probes were used to discriminate single-nucleotide polymorphism (SNP) genotypes in cohort genomic DNA: rs246240 (ABCC1), rs1476413 (MTHFR), rs2231142 (ABCG2), rs3740065 (ABCC2), rs4149081 (SLCO1B1), rs4846051 (MTHFR), rs10280623 (ABCB1), rs16853826 (ATIC), rs17421511 (MTHFR) and rs717620 (ABCC2). Mean plasma concentrations of methotrexate (MTX) and MTX-7-OH metabolites were higher (p < 0.05) at baseline in rs4149081 GA genotype patients. Patients with rs1476413 SNP TT or CT alleles have significantly higher (p < 0.001) plasma poly-glutamate metabolites at both study time points and correspondingly elevated disease activity scores. Patients with the rs17421511 SNP AA allele reported significantly lower pain scores (p < 0.05) at both study intervals. Genotyping strategies could help prioritise treatments to RA patients most likely to gain clinical benefit whilst minimizing toxicity. View Full-Text
Keywords: rheumatoid arthritis; SNP; DMARD; methotrexate; pharmacogenomics rheumatoid arthritis; SNP; DMARD; methotrexate; pharmacogenomics
Show Figures

Figure 1

MDPI and ACS Style

D’Cruz, L.G.; McEleney, K.G.; Tan, K.B.C.; Shukla, P.; Gardiner, P.V.; Connolly, P.; Conway, C.; Cobice, D.; Gibson, D.S. Clinical and Laboratory Associations with Methotrexate Metabolism Gene Polymorphisms in Rheumatoid Arthritis. J. Pers. Med. 2020, 10, 149.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop