甲氨蝶呤注射液所致药物不良反应与叶酰多聚谷氨酸合成酶和γ-谷氨酰水解酶基因多态性的相关性

发布时间：2018-05-17 02:45

本文选题：非霍奇金淋巴瘤 + 甲氨蝶呤　；参考：《中国临床药理学杂志》2016年21期

【摘要】：目的考察叶酰多聚谷氨酸合成酶(FPGS)rsl544105和γ-谷氨酰水解酶(GGH)rs3758149基因多态性与甲氨蝶呤(MTX)治疗非霍奇金淋巴瘤(NHL)所致药物不良反应的相关性。方法收集81例使用大剂量MTX化疗的NHL患者血样,用直接测序法检测FPGS rsl544105和GGH rs3758149基因多态性。用美国国立癌症中心通用药物不良反应术语标准统一评价MTX化疗后的药物不良反应。用SPPS软件分析FPGS rsl544105和GGH rs3758149基因多态性与MTX药物不良反应的相关性。结果 FPGS rsl544105位点GG、GA和AA基因的分布频率分别为6.17%,39.51%和54.32%,G和A等位基因的分布频率为25.93%和74.07%。GGH rs3758149位点CC、CT和TT基因的分布频率分别为65.43%,33.33%和1.23%,C和T等位基因的分布频率为82.10%和17.90%。FPGS rs1544105野生型(GG)和突变型(GA+AA)患者发生2级以上骨髓毒性和肝毒性的比例之间差异无统计学意义(P0.05)。GGH rs3758149野生型(CC)和突变型(CT+TT)患者发生2级以上中性粒细胞减少的比例分别为35.85%和10.71%,差异有统计学意义(P0.05)。结论 FPGS rsl544105可能与NHL患者MTX化疗后2级以上骨髓毒性和肝毒性发生率无相关性;而GGH rs3758149基因多态性与NHL患者MTX化疗后2级以上中性粒细胞减少发生率存在相关性。
[Abstract]:Objective to investigate the relationship between polymorphisms of FPGSN rsl544105 and gamma-glutamyl hydrolase GGHrs3758149 and adverse drug reactions induced by methotrexate (MTX) in the treatment of non-Hodgkin 's lymphoma. Methods Blood samples were collected from 81 patients with NHL who received high dose MTX chemotherapy. FPGS rsl544105 and GGH rs3758149 gene polymorphisms were detected by direct sequencing. Adverse drug reactions after MTX chemotherapy were evaluated uniformly using the National Cancer Center General adverse Drug reaction terminology. SPPS software was used to analyze the relationship between FPGS rsl544105 and GGH rs3758149 gene polymorphisms and adverse drug reactions in MTX. Results the frequencies of GGG GG and AA at FPGS rsl544105 locus were 6.179.51% and 54.32%, respectively. The frequencies of G and A alleles were 25.93% and 65.43 ~ 33.33% and 1.23C and T alleles were 82.10% and 65.43 ~ 33.33%, respectively. There was no significant difference in the proportion of grade 2 or more of bone marrow toxicity and hepatotoxicity between patients with 17.90%.FPGS rs1544105 wild type GG) and mutant GA-AAA. There was no significant difference in the incidence of grade 2 or more neutropenia in patients with 17.90%.FPGS rs1544105 wild type or GGH rs3758149. The ratio was 35.85% and 10.71% respectively, the difference was statistically significant (P 0.05). Conclusion FPGS rsl544105 may not be associated with the incidence of bone marrow toxicity and hepatotoxicity in patients with NHL above grade 2 after MTX chemotherapy, while the polymorphism of GGH rs3758149 gene is associated with the incidence of neutropenia above grade 2 after MTX chemotherapy in NHL patients.
【作者单位】：福建省肿瘤医院/福建医科大学附属肿瘤医院药剂科;
【基金】：国家临床重点专科建设基金资助项目(2013) 福建省自然科学基金资助项目(2016J01509) 福建省卫生厅青年科研课题基金资助项目(2013-1-8)
【分类号】：R733.1

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