1. Association between SNPs and hepatotoxicity in patients with primary central nervous system lymphoma on high-dose methotrexate therapy
- Author
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Shenghui Mei, Zhigang Zhao, Kefu Yu, Qing Zhao, Xiaohui Ren, Yong Cui, Chun Zeng, and Song Lin
- Subjects
Adult ,Central Nervous System ,Male ,medicine.medical_specialty ,Genotype ,Lymphoma ,MTHFD1 ,Pharmaceutical Science ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,030226 pharmacology & pharmacy ,Gastroenterology ,Formate-Tetrahydrofolate Ligase ,03 medical and health sciences ,0302 clinical medicine ,Cyclin D1 ,Asian People ,Aminohydrolases ,Multienzyme Complexes ,Internal medicine ,Odds Ratio ,medicine ,Humans ,In patient ,Aged ,Methylenetetrahydrofolate Dehydrogenase (NADP) ,Pharmacology ,business.industry ,Primary central nervous system lymphoma ,Thymidylate Synthase ,Middle Aged ,medicine.disease ,High dose methotrexate ,Introns ,Multidrug Resistance-Associated Protein 2 ,Methotrexate ,Liver ,030220 oncology & carcinogenesis ,Female ,Chemical and Drug Induced Liver Injury ,business ,medicine.drug - Abstract
Objectives This study aims to evaluate the association between polymorphisms of methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity in Chinese patients with primary central nervous system lymphoma. Methods Sixty-five patients in 411 treatment courses were enrolled and their toxicities were evaluated. The association between 30 candidate SNPs from 20 methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity was analysed by PLINK and logistic regression. Key findings TYMS 6 bp DI + II (rs151264360; OR, 0.41; 95% CI, 0.25–0.66; P = 0.00029), MTHFD1 1958 GA + AA (rs2236225; OR, 0.55; 95% CI, 0.33–0.91; P = 0.020) and CCND1 870 GA + GG (rs9344; OR, 0.42; 95% CI, 0.24–0.73; P = 0.0024) had less risk of hepatotoxicity compared with their homozygotes (DD, GG and AA, respectively), while ABCC2 intron 29 GA + GG (rs3740065; OR, 3.14; 95% CI, 1.89–5.20; P = 0.00001) was more prevalent in patients with hepatotoxicity than TT. Conclusions TYMS 6 bp DI + II, MTHFD1 1958 GA + AA, CCND1 870 GA + GG genotypes were associated with a lower probability of hepatotoxicity in patients with primary central nervous system lymphoma on high-dose methotrexate therapy, and ABCC2 intron 29 GA + GG was correlated with increased risk of hepatotoxicity.
- Published
- 2021
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