{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T13:35:34Z","timestamp":1780580134537,"version":"3.54.1"},"reference-count":0,"publisher":"Association of Basic Medical Sciences of FBIH","issue":"8","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomol Biomed"],"abstract":"<jats:p>Rheumatoid arthritis (RA) exhibits significant inter-patient variability in response to and toxicity from methotrexate (MTX). The clinical utility of erythrocyte methotrexate polyglutamates (MTXPGs) and MTX-pathway pharmacogenetics remains uncertain. This study investigates the relationships between MTX-pathway gene polymorphisms, erythrocyte MTXPG levels, and MTX treatment outcomes in RA.\u00a0In a single-center, cross-sectional cohort study conducted in southern Fujian from 2017 to 2020, we analyzed 140 Han Chinese RA patients who had been receiving stable low-dose oral MTX (7.5\u201315 mg\/week) for at least three months. Genotyping was performed using MassARRAY, and MTXPG levels 1\u20136 were quantified in red blood cells via LC-MS\/MS. Data on treatment efficacy (measured by ACR20 and clinical scales) and MTX-related adverse drug reactions (ADRs) were collected, with associations analyzed through univariate and multivariable models.\u00a0MTXPG levels 1\u20133 were detectable in all patients, while longer-chain MTXPGs were infrequent. The SLCO1B1\u00a0521T&gt;C polymorphism was independently associated with lower levels of MTXPG1 (B=\u22121.119), MTXPG2 (B=\u22120.924), and total MTXPG (B=\u22120.849), all with P-values \u22640.045. However, MTXPG levels did not correlate with MTX efficacy or ADRs. The GGH\u00a0401C&gt;T polymorphism was associated with a reduced ACR20 response (OR=0.421, p=0.021) and higher visual analog scale (VAS) and patient global assessment (PGA) scores. Additionally, the variants SLCO1B1\u00a0521T&gt;C and ABCB1\u00a03435C&gt;T were linked to higher scores in the Patient Health Global Assessment (PHGA) and Health Assessment Questionnaire (HAQ).\u00a0In this low-dose MTX cohort, erythrocyte MTXPGs did not predict clinical outcomes. However, variants in SLCO1B1, GGH, and ABCB1\u00a0emerged as exploratory candidate markers for MTX response, warranting validation in larger prospective cohorts.<\/jats:p>","DOI":"10.17305\/bb.2026.13544","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:31:01Z","timestamp":1768829461000},"page":"1334-1343","source":"Crossref","is-referenced-by-count":1,"title":["MTX pathway gene variants, erythrocyte methotrexate polyglutamates, and treatment outcomes in rheumatoid arthritis"],"prefix":"10.17305","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6624-5831","authenticated-orcid":false,"given":"Peihong","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuilv","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieli","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0526-3875","authenticated-orcid":false,"given":"Weiping","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6922","published-online":{"date-parts":[[2026,1,19]]},"container-title":["Biomolecules and Biomedicine"],"original-title":[],"link":[{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/13544\/4106","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/13544\/4106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T23:01:38Z","timestamp":1773961298000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/view\/13544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,19]]},"references-count":0,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,3,19]]}},"URL":"https:\/\/doi.org\/10.17305\/bb.2026.13544","relation":{},"ISSN":["2831-090X","2831-0896"],"issn-type":[{"value":"2831-090X","type":"electronic"},{"value":"2831-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1,19]]}}}