Genetic polymorphism of the methotrexate transporter ABCG2, blood pressure and markers of arterial function in patients with rheumatoid arthritis: repeated cross-sectional study

Leena R. Baghdadi, Richard J. Woodman, E. Michael Shanahan, Michael D. Wiese, Arduino A. Mangoni

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Abstract

Purpose: Methotrexate (MTX) treatment is associated with lower blood pressure (BP) and arterial stiffness in rheumatoid arthritis (RA). We investigated associations between single-nucleotide polymorphism (SNP) of the ATP-binding cassette efflux transporter gene ABCG2 (rs2231142), BP, and arterial stiffness in RA patients treated with MTX. Patients and methods: Clinical and 24-hour peripheral and central BP, arterial wave reflection (Augmentation Index, AIx), arterial stiffness (Pulse Wave Velocity, PWV), and intracellular MTX polyglutamate (MTXPGs) concentrations were assessed in 56 RA patients on stable treatment with MTX using a repeated cross-sectional study design with measurements at baseline and after 8 months. Results: Majority of the RA patients were homozygotes for the normal allele (CC, n=46) whereas 10 were rs2231142 heterozygotes (AC, n=10). MTXPGs concentrations were non-significantly higher in AC when compared to CC (144.3 vs 116.3 nmol/L packed RBCs, P=0.10). At baseline, the AC group had significantly lower age-adjusted clinical systolic BP (SBP) (P=0.01), 24-hour peripheral SBP (P=0.003), and central SBP (P=0.02) when compared to the CC group. However, AIx and PWV values were not significantly different between the two groups. When data from both visits were combined in a single analysis, and additionally adjusted for visit, gender, body mass index, and Disease Activity Score 28, the trend in SBP differences between-groups persisted but was no longer significant. Conclusion: Future studies are required to test the hypothesis that this genetic polymorphism is associated with lower BP, arterial stiffness, and possibly, cardiovascular risk, in RA patients treated with MTX.

Original languageEnglish
Pages (from-to)205-210
Number of pages6
JournalPharmacogenomics and Personalized Medicine
Volume11
DOIs
Publication statusPublished - 12 Nov 2018

Bibliographical note

CC BY-NC (unported v3.0) Open Access article licensed under a Creative Commons Attribution Non-Commercial license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/3.0/

Keywords

  • Methotrexate
  • disease-modifying antirheumatic drugs
  • blood presure
  • augmentation index
  • rheumatoid arthritis
  • pulse wave velocity
  • single-nucleotide polymorphisms
  • ATP-binding cassette transporters
  • ABCG2

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