{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T14:28:47Z","timestamp":1778336927636,"version":"3.51.4"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6]]},"abstract":"\n Objectives<\/jats:title>\n Genetic polymorphisms in FPGS<\/jats:italic>, MTHFR<\/jats:italic>, and ATIC<\/jats:italic> have emerged as important modulators of methotrexate (MTX) metabolism and toxicity. We investigated the distribution of FPGS<\/jats:italic> rs10106, MTHFR<\/jats:italic> rs1801131, and ATIC<\/jats:italic> rs2372536 polymorphisms in children with acute lymphoblastic leukemia (ALL) and assessed their influence on MTX concentrations, toxicity profiles, and clinical outcomes.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Genotyping of FPGS<\/jats:italic> rs10106 G\u2005>\u2005A, MTHFR<\/jats:italic> rs1801131 A\u2005>\u2005C, and ATIC<\/jats:italic> rs2372536 C\u2005>\u2005G polymorphisms was conducted using the Sequenom MassARRAY iPLEX platform in 145 pediatric ALL patients.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Significant ethnic differences were observed in the allelic and genotypic distributions of the three single nucleotide polymorphisms (SNPs) investigated. None of these three SNPs had a significant effect on MTX levels or toxicities. The frequencies of the ATIC<\/jats:italic> rs2372536 CC genotype and C allele in ALL patients (44.8% and 68.6%, respectively) were significantly lower than those in Han Chinese in Beijing, China (58.3% and 78.2%, respectively; P<\/jats:italic>\u2005=\u20050.036 and 0.019, respectively). Patients carrying the ATIC<\/jats:italic> rs2372536 GG genotype (36.4%, 4\/11) had a significantly higher relapse rate than the CC genotype carriers (6.2%, 4\/65, P<\/jats:italic>\u2005=\u20050.013). There, however, were no significant effects on relapse-free survival in Kaplan\u2013Meier and Cox regression analyses for all three candidate SNPs.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our findings offer valuable insights into the intricate interplay between genetic polymorphisms, MTX exposure, toxicities, and clinical outcomes in patients with ALL and have the potential to inform precision medicine strategies.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000563","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T13:02:59Z","timestamp":1740402179000},"page":"127-135","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["The impact of genetic variations in FPGS, MTHFR, and ATIC on methotrexate response among pediatric patients with acute lymphoblastic leukemia"],"prefix":"10.1097","volume":"35","author":[{"given":"Shu-Mei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University"},{"name":"Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan-Qi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University"},{"name":"Department of Clinical Pharmacy, College of Pharmacy, Capital Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Yan","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Armed Police Beijing Corps Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Beijing Shijitan 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