中国药房2024，Vol.35Issue(1)：80-83,4.DOI:10.6039/j.issn.1001-0408.2024.01.14
MTHFR基因多态性对骨肉瘤患者首次应用大剂量甲氨蝶呤后不良反应的影响
Effects of MTHFR gene polymorphism on the adverse reactions in osteosarcoma patients after the first high-dose methotrexate treatment
摘要
Abstract
OBJECTIVE To explore the effects of 5,10-methylenetetetrahydrofolate reductase(MTHFR)gene polymorphism on the adverse reactions in patients with osteosarcoma after the first high-dose methotrexate(HD-MTX)treatment.METHODS A prospective study was conducted to include 53 patients with osteosarcoma treated with HD-MTX at the first admission in General Hospital of Eastern Theater Command.The dose of MTX was evaluated according to the polymorphism of rs1801133 in the METHFR gene and demographic factors,then whole pharmaceutical monitoring was conducted.The data on liver toxicity,renal toxicity,hematological toxicity,and gastrointestinal reaction were collected after the first chemotherapy cycle.Single factor analysis and binary Logistic regression analysis were used to analyze the correlation between MTX dose,24 h blood drug concentration,and rs1801133 locus genotype with four adverse reactions.RESULTS The MTX dosage in patients with CC wild type was significantly higher than that in TT mutant type(7.97 g/m2 vs.6.98 g/m2,P=0.030),but this difference did not affect the 0 h and 24 h blood drug concentrations of MTX.The above four adverse reactions were not related to the dose of MTX.The results of binary Logistic regression analysis showed that carrying one T allele increased the risk of developing hematological toxicity by 4.13 times(95%confidence interval:1.35-12.62,P=0.013).When 24 h plasma concentration threshold of MTX was set to 2.65 µmol/L,the sensitivity and specificity of predicting liver function damage were 53.33%and 86.96%,respectively;when the threshold was set to 7.28 μmol/L,the sensitivity and specificity of predicting renal damage were 100%and 81.63%.CONCLUSIONS The polymorphism of the rs1801133 in the MTHFR gene is associated with hematological toxicity of MTX.Patients who take HD-MTX for the first time and carry the T allele have a high risk of hematological toxicity.The 24 h plasma concentration of MTX is related to liver toxicity and renal toxicity.In addition,monitoring the 24 h blood drug concentration can predict liver and renal toxicity,and take early intervention measures.关键词
甲氨蝶呤/大剂量/亚甲基四氢叶酸还原酶/rs1801133位点/不良反应/基因多态性Key words
methotrexate/high-dose/5,10-methylenete-trahydrofolate reductase/rs1801133 locus/adverse reactions/genetic polymorphism分类
医药卫生引用本文复制引用
初亚男,张婕妤,封利颖,张晏洁,刘雪姣..MTHFR基因多态性对骨肉瘤患者首次应用大剂量甲氨蝶呤后不良反应的影响[J].中国药房,2024,35(1):80-83,4.基金项目
东部战区总医院临床诊疗新技术项目(No.22LCZLXJS56) （No.22LCZLXJS56）
