论文部分内容阅读
目的评价亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因多态性在甲氨喋呤治疗急性淋巴细胞白血病过程中毒副反应的相关性。方法通过计算机检索国内外相关数据库:Pub Med,EMBASE,CNKI,维普中文科技期刊数据库以及万方数据库,语种不限。纳入符合标准的病例-对照研究,然后应用STATA 12.0软件进行Meta分析,合并优势比(OR)和95%的可信区间(95%CI),并且进行异质性检验和发表偏倚的评估。结果总共纳入12项研究,840名病例,其中MTHFR C677T研究的文献有12篇,只有其中的8篇是关于MTHFR A1298C的研究。MTHFR C677T多态性与总体毒性(TT vs.CC+CT:OR=3.21,95%CI:1.02~10.13,P=0.047)、贫血(TT vs.CC+CT:OR=1.92,95%CI:1.01~3.66,P=0.046)、骨髓抑制(TT vs.CC+CT:OR=3.52,95%CI:1.39~8.92,P=0.008)、胃肠道反应(TT vs.CC+CT:OR=5.09,95%CI:1.32~19.62,P=0.018)和皮疹(TT+CT vs.CC:OR=3.34,95%CI:1.09~10.18,P=0.034)有密切关系。A1298C在总体毒性(CC+AC vs.AA:OR=0.20,95%CI:0.09~0.45,P<0.001)的模型比较中差异有统计学意义。结论与677CC+CT相比,突变基因型677TT更容易导致毒性反应的发生。A1298C突变型基因1298CC+AC在总体毒性上呈现出一定的保护作用。
Objective To evaluate the association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with the toxicity of methotrexate in the treatment of acute lymphoblastic leukemia. Methods The databases of Pub Med, EMBASE, CNKI, VIP Chinese Sci - tech Periodical Database and Wanfang Database were searched by computer. A well-matched case-control study was included. Meta-analysis was then performed using STATA 12.0 software and the odds ratio (OR) and 95% confidence interval (95% CI) were combined and assessed for heterogeneity and publication bias. Results A total of 12 studies, 840 cases, were included, of which 12 were reported in the MTHFR C677T study and only 8 of them were studies on MTHFR A1298C. MTHFR C677T polymorphism and overall toxicity (TT vs. CC + CT: OR = 3.21, 95% CI: 1.02-10.13, P = 0.047) (TT vs. CC + CT: OR = 3.52, 95% CI: 1.39-9.92, P = 0.008), gastrointestinal reaction 5.09, 95% CI: 1.32-19.62, P = 0.018) and rash (TT + CT vs. CC: OR = 3.34, 95% CI: 1.09 to 10.18, P = 0.034). A1298C had statistically significant difference in the model of overall toxicity (CC + AC vs.AA: OR = 0.20, 95% CI: 0.09-0.45, P <0.001). Conclusion Compared with 677CC + CT, the mutant genotype 677TT is more likely to cause toxic reactions. The A1298C mutant gene 1298CC + AC showed some protective effects on the overall toxicity.