Red blood cell folate concentrations and polyglutamate distribution in juvenile arthritis: predictors of folate variability

Pharmacogenetics and Genomics
M L BeckerJames S Leeder

Abstract

Methotrexate (MTX) has several enzymatic targets in the folate pathway. To better understand the variability in response to MTX, we characterized the interindividual variability of intracellular folate pools in children with juvenile arthritis (JA) and determined clinical and genetic contributors to this variability. This exploratory single-center cross-sectional study evaluated 93 patients with JA not currently receiving MTX. Whole blood, plasma, and erythrocyte folate concentrations were determined after deconjugation and analyzed through reversed-phase separation and stable isotope dilution tandem mass spectrometry. Folate polyglutamates were measured in red blood cell lysates using an ion-pair reversed phase chromatography tandem mass spectrometry method. Intracellular concentrations of 5-methyl-tetrahydrofolate (5-CH3-THF) and 5,10-methenyl-tetrahydrofolate varied approximately 20-fold and 80-fold, respectively. The polyglutamated forms of 5-CH3-THF as a percentage of total 5-CH3-THF (5-CH3-THFGlun) were also measured. Hierarchical clustering of 5-CH3-THFGlun revealed two groups, each with two distinct clusters. There was an inverse relationship between 5-CH3-THFGlun chain length and plasma 5-CH3-THF concentrations. A subg...Continue Reading

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Citations

Nov 19, 2013·Pharmacogenomics·Adam StevensPeter Clayton
Jun 30, 2014·Best Practice & Research. Clinical Rheumatology·Elizabeth A Kessler, Mara L Becker
Dec 11, 2013·Bioanalysis·Leon van Haandel, John F Stobaugh
Aug 31, 2013·The Biochemical Journal·Manuel Gutiérrez-Aguilar, Christopher P Baines
Jun 16, 2016·Pediatric Rheumatology Online Journal·J FráňováP Doležalová
Jul 2, 2019·Journal of Pediatric Hematology/oncology·Pooja Kandikonda, Bruce Bostrom
Nov 30, 2013·Annals of the Rheumatic Diseases·Maja Bulatović ĆalasanNico M Wulffraat
Jun 27, 2012·Current Opinion in Rheumatology·Mara L Becker

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