Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies.
Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies.
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ABCB1 和 MTHFR 多态性对成人血液恶性肿瘤甲氨蝶呤相关毒性的影响
DOI：
10.3389/fonc.2021.759805
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发表时间：
2021
影响因子：
4.7
通讯作者：
Hong ZY
中科院分区：
文献类型：
--
作者：
Han J;Liu L;Meng L;Guo H;Zhang J;Han ZQ;Hong ZY
甲氨蝶呤 (MTX) 途径基因的单核苷酸多态性 (SNP) 与血液恶性肿瘤治疗中 MTX 相关毒性之间的关联研究很受欢迎。在这里，我们研究了 157 名诊断为血液恶性肿瘤的中国成年患者中 MTHFR 和 ABCB1 的 SNP 与 MTX 相关毒性之间的关联。通过荧光原位杂交对患者进行 MTHFR rs1801131、MTHFR rs1801133 和 ABCB1 rs1045642 基因分型。与CC基因型患者相比，MTHFR rs1801133T等位基因患者发生造血毒性的风险显着较高（p=0.003）。对于MTHFR rs1801131，CC和AC基因型患者的造血毒性频率显着低于AA基因型患者（p=0.044）。总之，我们确定了 ABCB1 和 MTHFR 的 SNP 对患有血液恶性肿瘤的成人 MTX 相关造血毒性的重要影响。为了优化大剂量（HD）-MTX治疗并降低相关造血毒性，有必要在开始HD-MTX前检测MTHFR和ABCB1的SNP，并根据成人血液系统恶性肿瘤的基因检测和疾病类型决定MTX的最佳剂量和亚叶酸救援时间。
Study of the association between single nucleotide polymorphisms (SNPs) of methotrexate (MTX) pathway genes and MTX-related toxicity in the treatment of hematological malignancies is popular. Here, we studied the association between SNPs of MTHFR and ABCB1 and MTX-related toxicity in 157 adult Chinese patients diagnosed with hematological malignancies. Patients were genotyped for MTHFR rs1801131, MTHFR rs1801133, and ABCB1 rs1045642 by fluorescence in situ hybridization. Patients with MTHFR rs1801133T allele had a significantly higher risk of hematopoietic toxicity compared with those with CC genotype (p=0.003). With respect to MTHFR rs1801131, patients with CC and AC genotypes had significantly lower frequency of hematopoietic toxicity than patients with AA genotype (p=0.044). In conclusion, we identified an important influence of the SNPs of ABCB1 and MTHFR on MTX-related hematopoietic toxicity in adults with hematological malignancies. To optimize high-dose (HD)-MTX therapy and reduce related hematopoietic toxicity, it is necessary to detect the SNPs of MTHFR and ABCB1 before initiating HD-MTX and deciding the optimal dose of MTX and duration of leucovorin rescue, according to genetic tests and disease type in adults with hematological malignancies.
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影响因子：
3.8
作者：
Elmore, C. Lee;Wu, Xuchu;Matthews, Rowena G.
通讯作者：
Matthews, Rowena G.
影响因子：
2.6
作者：
Mikkelsen TS;Thorn CF;Yang JJ;Ulrich CM;French D;Zaza G;Dunnenberger HM;Marsh S;McLeod HL;Giacomini K;Becker ML;Gaedigk R;Leeder JS;Kager L;Relling MV;Evans W;Klein TE;Altman RB
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Altman RB
影响因子：
45.3
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Bhojwani, Deepa;Sabin, Noah D.;Relling, Mary V.
通讯作者：
Relling, Mary V.
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1.4
作者：
Raoufi A;Rahimi Kelarijani B;Ahadi HR;Hassani Derakhshandeh B;Nooroollahzadeh Z;Hajifathali A
通讯作者：
Hajifathali A
影响因子：
2.7
作者：
Chiusolo, Patrizia;Reddiconto, Giovanni;Sica, Simona
通讯作者：
Sica, Simona