Effects of genetic polymorphisms on methotrexate levels and toxicity in Chinese patients with acute lymphoblastic leukemia

被引：7

作者：

Hao, Qishan ^{[1
]}

Song, Yang ^{[1
]}

Fang, Qiuyun ^{[1
]}

Lin, Yani ^{[2
]}

Chen, Long ^{[2
]}

Wang, Xiaodan ^{[1
]}

Zhang, Ping ^{[1
]}

Wang, Zhe ^{[1
]}

Gong, Xiaoyuan ^{[1
]}

Liu, Kaiqi ^{[1
]}

Li, Qinghua ^{[1
]}

Tian, Zheng ^{[1
]}

Wang, Min ^{[1
]}

Wang, Jianxiang ^{[1
]}

Mi, Yingchang ^{[1
,3
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Haihe Lab Cell Ecosyst, State Key Lab Expt Hematol,Natl Clin Res Ctr Blood, Tianjin, Peoples R China

[2] SINO US Diagnost Lab, Tianjin, Peoples R China

[3] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Haihe Lab Cell Ecosyst, State Key Lab Expt Hematol,Natl Clin Res Ctr Blood, 288 Nanjing Rd, Tianjin, Peoples R China

来源：

BLOOD SCIENCE | 2023年 / 5卷 / 01期

关键词：

Acute lymphoblastic leukemia; Concentration; Methotrexate; Polymorphism; Toxicity; HIGH-DOSE METHOTREXATE; ABCC2; POLYMORPHISMS; PLASMA METHOTREXATE; CHILDREN; THERAPY; IMPACT;

D O I：

10.1097/BS9.0000000000000142

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Methotrexate (MTX) has an antitumor effect when used for the treatment of acute lymphoblastic leukemia (ALL). This study aims at evaluating the associations between 14 polymorphisms of six genes involved in MTX metabolism with serum MTX concentration and toxicity accompanying high-dose MTX. Polymorphisms in 183 Chinese patients with ALL were analyzed using TaqMan single nucleotide polymorphism genotyping assay. The serum MTX concentration was determined using homogeneous enzyme immunoassay. MTX-related toxicities were also evaluated. Renal toxicity was significantly associated with higher serum MTX concentrations at 24, 48, and 72 hours, and MTX elimination delay (P = 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively), whereas SLCO1B1 rs4149056 was associated with serum MTX concentrations at 48 and 72 hours, and MTX elimination delay in candidate polymorphisms (P = 0.014, P = 0.019, and P = 0.007, respectively). SLC19A1 rs2838958 and rs3788200 were associated with serum MTX concentrations at 24 hours (P = 0.016, P = 0.043, respectively). MTRR rs1801394 was associated with serum MTX concentrations at 72 hours (P = 0.045). Neutropenia was related to SLC19A1 rs4149056 (odds ratio [OR]: 3.172, 95% confidence interval [CI]: 1.310-7.681, P = 0.011). Hepatotoxicity was associated with ABCC2 rs2273697 (OR: 3.494, 95% CI: 1.236-9.873, P = 0.018) and MTRR rs1801394 (OR: 0.231, 95% CI: 0.084-0.632, P = 0.004). Polymorphisms of SLCO1B1, SLC19A1, ABCC2, and MTRR genes help predict higher risk of increased MTX levels or MTX-related toxicities in adult ALL patients.

引用

页码：32 / 38

页数：7

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