Effects of SHMT1 rs1979277 genetic polymorphisms on serum concentrations and adverse reactions of methotrexate in children with acute lymphoblastic leukemia
10.19405/j.cnki.issn1000–1492.2026.02.015
- VernacularTitle:急性淋巴细胞白血病儿童SHMT1 rs1979277位点遗传多态性对甲氨蝶呤血清浓度和不良反应的影响
- Author:
Lingjia MENG
1
;
Sihan LIU
1
;
Miao LI
1
;
Shumei WANG
1
Author Information
1. Department of Pharmacy， Beijing Shijitan Hospital， Capital Medical University， Beijing 100038
- Publication Type:Journal Article
- Keywords:
acute lymphoblastic leukemia;
serine hydroxymethyltransferase 1;
genetic variation;
methotrexate;
adverse event;
prognosis
- From:
Acta Universitatis Medicinalis Anhui
2026;61(2):292-300
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effects of serine hydroxymethyltransferase 1 （SHMT1） rs1979277 polymorphisms on pharmacokinetic characteristics and clinical prognosis of methotrexate （MTX） in children with acute lymphoblastic leukemia （ALL）. MethodsMatrix-assisted laser desorption/ionization time of flight mass spectrometry was used for SHMT1 rs1979277 genotyping in children with ALL . Clinical data including serum MTX concentrations， incidences of adverse events， and ALL relapse after chemotherapy with MTX were collected. The associations of SHMT1 rs1979277 G>A genotypes with dose-adjusted serum concentrations （C/D ratios）， adverse events of MTX， and relapse were analyzed. The associations between rs1979277 genotypes and SHMT1 expression were explored based on Bioinformatics methods. ResultsAmong the 146 children with ALL included， the rs1979277 GG homozygous genotype accounted for 85.62% （125/146）， while the GA heterozygous genotype accounted for 14.38% （21/146）. The frequency of the G allele was 92.81% （271/292）， while the A allele was only 7.19% （21/292）. Children with the GG homozygous genotype had higher median C/D ratios of MTX in 24 h ［12.06 （μmol·m2）/（L·g）］ and higher relapse rates （12.80%） than those in GA heterozygous genotype carriers ［10.96 （μmol·m2）/（L·g）， and 9.52%， respectively］. However， none of the above differences were statistically significant （all P>0.05）. The incidences of respiratory （19.05%） and liver disorders （33.33%） in children with the GA heterozygous genotype were significantly higher than those in GG homozygous genotype carriers （4.00% and 12.00%， respectively， P<0.05）. There were no statistically significant differences in the incidences of other adverse events. Bioinformatics analysis showed that the rs1979277 A allele was significantly associated with higher SHMT1 expression in multiple tissues， such as the tibial artery， pancreas， and adrenal gland （P<0.05）. ConclusionSHMT1 rs1979277 GA genotype may be a risk factor for respiratory and liver disorders in ALL children treated with MTX.
