Association of MTHFR and ABCB1 polymorphisms with MTX‐induced mucositis in Chinese paediatric patients with acute lymphoblastic leukaemia, lymphoma or osteosarcoma—A retrospective cohort study. (4th August 2021)

• Record Type: Journal Article
• Authors: Gong, Yan; Luo, Li; Wang, Liu; Chen, Jun; Chen, Fen; Ma, Yuanyuan; Xu, Zhen; Sun, Yiqi; Luo, Lin; Shi, Chen; Li, Xingang
• Is Part Of: Journal of clinical pharmacy and therapeutics. Volume 46:Number 6(2021)
• Page Start: 1557
• Page End: 1563
• Publication Date: 2021-08-04
• Subjects: genetic polymorphisms -- methotrexate -- mucositis -- toxicity; Clinical pharmacology -- Periodicals; Chemotherapy -- Periodicals; 615
• DOI: 10.1111/jcpt.13505
• Languages: English
• ISSNs: 0269-4727

Abstract

Abstract: What is known and objective: MTX pharmacology and toxicity involve several metabolizing enzymes and transporters whose functions have been suggested to be altered by genetic polymorphisms. The current study is to investigate the relationship between the genetic variation and MTX‐induced adverse drug effects. Methods: A total of 80 paediatric patients (aged 1–14 years) were enrolled in this study. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 scoring system. Genotyping was performed by MassARRAY Assay method. Data were analysed using Spss statistical package version 17.0 and Plink v1.07 software. The HWE was tested by a chi‐square test. The Fisher's exact test (chi‐squaretest) was used to compare the distributions of genotypes between cases and controls. OR and 95%CI were applied to evaluate the association of genetic variants with the presence of mucositis using unconditional logistic regression. Results and discussion: Mucosal inflammatory injuries were found in 28 children. SNPs of rs1128503 ( p = 0.0022, OR = 3.04, 95%CI = 1.39–6.64) and rs1045642 ( p = 0.0052, OR = 2.38, 95%CI = 1.15–5.00) located in the gene of ABCB1 and SNPs of rs1801133 ( p = 0.040, OR = 2.50, 95%CI = 1.06–5.88) located in the gene of MTHFR show marked impacts on the risk of developing mucositis. What is new and conclusion: SNPs of ABCB1 rs1128503, rs1045642 and MTHFR rs1801133 can be risk predictor for MTX‐induced mucositis in Chinese paediatric patients diagnosed with acute lymphoblastic leukaemia, lymphoma or osteosarcoma. Abstract : ABCB1 and MTHFR polymorphisms can be risk predictors for MTX‐induced mucositis in pediatric patients.