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Is Pharmacogenetic Panel Testing Applicable to Low-Dose Methotrexate in Rheumatoid Arthritis? - A Case Report.
JournalItem (Reviews, Editorials, Rezensionen, Urteilsanmerkungen etc. in einer wissenschaftlichen Zeitschrift)
 
ID 4647351
Author(s) Jeiziner, Chiara; Allemann, Samuel S; Hersberger, Kurt E; Meyer Zu Schwabedissen, Henriette E
Author(s) at UniBasel Allemann, Samuel
Meyer zu Schwabedissen, Henriette
Year 2022
Title Is Pharmacogenetic Panel Testing Applicable to Low-Dose Methotrexate in Rheumatoid Arthritis? - A Case Report.
Journal Pharmacogenomics and personalized medicine
Volume 15
Pages 465-475
Keywords ABCB1; MTHFR; MTX; PGx; SLC19A1; methotrexate; pharmacogenetics; rheumatoid arthritis
Abstract

Pharmacogenetic (PGx) panel testing could help to determine the heritable component of a rheumatoid arthritis (RA) patient's susceptibility for therapy failure and/or adverse drug reactions (ADRs) from methotrexate (MTX). Considering the literature mentioning the potential applicability of PGx panel testing within MTX regimens, we discuss the case of a patient who was treated with MTX, suffered from ADRs, and obtained a reactive PGx panel testing.; We used a commercial PGx panel test involving the ABC-transporters P-glycoprotein (P-gp; gene:; ABCB1; ), and breast cancer resistance protein (BCRP; gene:; ABCG2; ), the solute carriers reduced folate carrier 1 (RFC1; gene:; SLC19A1; ), and organic anion transporting polypeptide 1B1 (OATP1B1; gene:; SLCO1B1; ), and the enzymes inosine triphosphatase (ITPA), and glutathione transferase P1 (GSTP1). In addition, we genotyped the patient for the enzymes 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICAR)/inosine monophosphate (IMP) cyclohydrolase (gene name:; ATIC; ), gamma-glutamyl hydrolase (gene name:; GGH; ) and methylenetetrahydrofolate reductase (gene name:; MTHFR; ).; The PGx profile of the patient revealed genetic variants in SLC19A1, ABCB1, and MTHFR, which may explain the ADRs experienced during the treatment with MTX and a potentially lower efficacy of MTX. Based on our interpretation of the PGx profile, we recommended the patient to avoid MTX in the future.; The MTX pathway is complex, which makes the interpretation of genetic variants affecting metabolism challenging. A reactive PGx panel test was applicable to explain ADRs experienced during MTX treatment for a patient with RA. However, the clinical utility of PGx-guided MTX treatment in a primary care setting is still limited. In order to base a recommendation for MTX on PGx data, we need genome-wide association studies, large prospective multicenter studies and PGx studies, which analyze different multi-gene haplotypes and gene-drug-drug interactions for MTX.

ISSN/ISBN 1178-7066
Full Text on edoc
Digital Object Identifier DOI 10.2147/PGPM.S354011
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/35586477
   

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