Effect of single nucleotide polymorphisms on methotrexate-induced myelosuppression in patients with primary central nervous system lymphoma

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Author: Zhuo WU ¹ Xin YAO ² Tian-Ling DING ³ Bin WANG ¹ Ming-Kang ZHONG ¹  Xiao-Yan QIU ¹

Affiliation: 1. Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200040, China 2. School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China 3.Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, China

Keywords: Methotrexate Primary central nervous system lymphoma Myelosuppression Single nucleotide polymorphism Individualized drug therapy

DOI: 10.19960/j.issn.1005-0698.202310001

Reference: Zhuo WU, Xin YAO, Tian-Ling DING, Bin WANG, Ming-Kang ZHONG, Xiao-Yan QIU.Effect of single nucleotide polymorphisms on methotrexate-induced myelosuppression in patients with primary central nervous system lymphoma[J].Yaowu Liuxingbingxue Zazhi,2023, 32(10): 1081-1088.DOI: 10.19960/j.issn.1005-0698.202310001.[Article in Chinese]  Copied

Abstract
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Abstract

Objective To investigate the effect of single nucleotide polymorphisms of six related genes SLCO1B1, SLC19A1, ABCC2, ABCB1, FPGS, and GGH in the pathway of methotrexate (MTX) action on the adverse effects of myelosuppression caused by MTX in patients with primary central nervous system lymphoma (PCNSL).

Methods DNA samples from 121 patients with PCNSL were genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Patient demographics and corresponding clinical information were obtained from the electronic medical record system. The χ² test and multivariate logistic regression analysis were used to explore the effect of single nucleotide polymorphisms on the patients' myelosuppression after chemotherapy, respectively.

Results In 121 patients with a total of 508 courses, 186 courses (36.6%) experienced myelosuppressive adverse reactions. Single factor analysis showed that the single nucleotide polymorphisms of SLCO1B1 rs2306283 and GGH rs2305558 had an effect on the incidence of myelosuppression due to MTX (P<0.05). Logistic regression analysis showed that the SNP of SLCO1B1 rs2306283 still had an effect on the incidence of MTX-induced myelosuppression (OR=1.542, 95%CI: 1.040 to 2.287, P=0.031).

Conclusion The GG genotype of SLCO1B1 rs2306283 may serve as an independent risk factor for predicting MTX-induced myelosuppression and provide basis for individualized drug therapy of MTX.

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