亚甲基四氢叶酸还原酶基因多态性与急性淋巴细胞白血病患者甲氨蝶呤化疗药物不良反应的相关性研究

发布时间：2018-02-04 05:14

本文关键词： 亚甲基四氢叶酸还原酶基因多态性大剂量甲氨蝶呤药物不良反应　出处：《中国临床药理学杂志》2017年17期 　论文类型：期刊论文

【摘要】：目的探讨急性淋巴细胞白血病(ALL)患者的亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与大剂量甲氨蝶呤(HD-MTX)化疗药物不良反应的相关性。方法收集93例ALL患者血样,用试剂盒法提取血液DNA,用聚合酶链式反应-芯片杂交技术检测MTHFR C677T基因多态性,用酶放大免疫分析法(EMIT)测定患者MTX血药浓度,收集患者HD-MTX化疗期间的临床资料,并观察记录患者HD-MTX化疗后相关药物不良反应。结合MTHFR C677T基因分型结果,用方差分析、非线性Logistic回归分析MTHFR C677T基因多态性与HD-MTX化疗后药物不良反应的关系。结果 MTHFR C677T各基因型间口腔黏膜损害的发生率差异有统计学意义(P0.05),MTHFR 677CT/TT基因型者发生口腔黏膜损害的风险较CC基因型者显著性增高,CT基因型者发生口腔黏膜损伤的风险是CC基因型者的2.81倍(OR=2.81,95%CI:1.06~7.40,P0.05),TT型是CC型的5.53倍(OR=5.53,95%CI:1.58~19.27,P0.05)。MTHFR C677T各基因型间Ⅱ级以上骨髓抑制的发生率差异有统计学意义(P0.05),TT型发生Ⅱ级以上骨髓抑制的风险是CC型的3.75倍(OR=3.75,95%CI:1.14~12.40,P0.05);MTHFR C677T各基因型在HD-MTX给药后48 h的血药浓度差异有统计学意义(P0.05)。结论 MTHFR C677T基因多态性影响ALL患者HD-MTX化疗期间MTX血药浓度,与口腔黏膜损害、骨髓抑制存在一定相关性。
[Abstract]:Objective to investigate the acute lymphoblastic leukemia (ALL) patients with methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and high-dose methotrexate (HD-MTX) chemotherapy drug related adverse effects. Methods 93 ALL patients were collected blood samples, blood DNA extracted by kit method, reaction for detection of MTHFR polymorphism of C677T gene chip hybridization with polymerase chain using radioimmunoassay, enzyme amplification (EMIT) assay in patients with MTX serum concentration, clinical data were collected during HD-MTX chemotherapy, and adverse drug reactions were observed and recorded after HD-MTX chemotherapy. Combined with the classification results of MTHFR C677T gene, using variance analysis, the relationship between adverse drug reaction and nonlinear Logistic regression analysis of MTHFR C677T gene polymorphism and after HD-MTX chemotherapy. Results MTHFR C677T genotypes between the oral mucosa damage rate was statistically significant (P0.05), MTHFR 677CT/TT The risk genotype incidence of oral mucosal injury compared with CC genotype significantly increased the risk of oral mucosal injury of CT genotype was 2.81 times of the CC genotype (OR=2.81,95%CI:1.06~7.40, P0.05), TT is 5.53 times that of the CC genotype (OR=5.53,95%CI:1.58~19.27, P0.05).MTHFR C677T genotypes between grade the incidence of myelosuppression was statistically significant (P0.05), TT risk grade of bone marrow suppression is 3.75 times of type CC (OR=3.75,95%CI:1.14~12.40, P0.05); MTHFR C677T genotypes in HD-MTX after administration of different blood drug concentration of 48 h was statistically significant (P0.05). Conclusion the effect of MTHFR C677T gene the polymorphism of ALL patients during chemotherapy of HD-MTX MTX blood concentration, and oral mucosa damage, there is a certain correlation between bone marrow suppression.

【作者单位】：新疆医科大学第一附属医院药学部;
【基金】：新疆维吾尔自治区卫生厅青年科技人才专项科研基金资助项目(2014Y23)
【分类号】：R733.71
【正文快照】： (新疆医科大学第一附属医院药学部,乌鲁木齐830011)LI Jing,WANG Jie,YU Chang-zhi,ZHAO Jun,YUAN Yuan,CHEN Bo-song,WANG Jian-hua(Department of Pharmacy,The FirstAffiliated Hospital of Xinjiang MedicalUniversity,Urumqi 830011,China)用大剂量甲氨蝶呤(HD-MTX)联合

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