Effects of polymorphisms of MTHFR and ABCB1 on serum concentration and adverse reactions of methotrexate in patients with hematological malignancies

JIANG Yan; HU Nan; LING Jing; YANG Xuping; ZOU Sulan; HE Yutian; DONG Lulu

Abstract：Objective:To investigate the effects of methylenetetrahydrofolate reductase(MTHFR)and ATP bind-ing cassette transporter(ABC)gene polymorphisms on the serum concentration and adverse reactions of high-dose methotrexate(MTX)in the treatment of hematological malignancies.Methods:A total of 42 patients with hematologi-cal malignancies who were admitted to the First People's Hospital of Changzhou from July 2020 to December 2021 were selected.Fluorescence in situ hybridization was used to determine the type of MTHFR 677(677 C＞T),MTHFR 1298(1298 A＞C),ABCB1(3435 C＞T)and blood concentration information and clinical data during medication were col-lected.The correlation between MTHFR and ABCB1 gene polymorphism and MTX plasma concentration and adverse reactions was analyzed.Results:There were no significant differences in the plasma concentrations of MTHFR(6 7 7 C＞T)at24h,48h,and72h(P＞0.05).The24-hourplasma concentrations of AC+CC typeof MTHFR(1 2 98 A＞C)were significantly higher than those of AA type(P＜0.05),while the 24-hour plasma concentrations of AB-CB1(3435 C＞T)homozygous mutant TT type were significantly higher than those of CC type and CT type,and the blood concentration of TT type 48hMTX was significantly higher than that of CT type(P＜0.05).There was no sig-nificant difference in the risk of adverse reactions among patients with different genotypes of MTHFR(677 C＞T),while MTHFR(1298 A＞C)and ABCB1(3435 C＞T)were associated with the risk of some adverse reactions(P＜0.05).Conclusion:MTHFR(1298 A＞C)and ABCB1(3435 C＞T)gene polymorphisms are significantly correlated with MTX plasma concentration and some adverse reactions after HD-MTX chemotherapy,which can be used to guide the individualized therapy of patients with hematological tumors.