摘要
目的考察急性淋巴细胞白血病(ALL)患儿MTHFR rs1801131 A> C基因多态性对临床预后和甲氨蝶呤(MTX)化疗毒性的影响。方法收集134例ALL患儿的外周血,提取基因组DNA,用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术分析MTHFR rs1801131 A> C基因型。结果 MTHFR rs1801131 CC基因型患儿的平均无事件生存间期(EFI)为26. 83个月,显著长于AC基因型患儿(15. 72个月,P <0. 05),CC基因型患儿的复发率(0)低于AA(9. 37%)和AC(12. 50%)基因型患儿,但差异无统计学意义。除了肝和电解质不良事件在CC基因型患儿中的发生率(33. 33%和16. 67%)高于AA(12. 50%和14. 58%)和AC(18. 75%和3. 13%)基因型患儿以外,其余不良事件在CC基因型患儿中的发生率低于AA和AC基因型患儿,3种基因型之间的MTX化疗毒性发生率差异无统计学意义。结论 MTHFR rs1801131 A> C基因多态性与ALL患儿临床预后显著相关,但与MTX化疗毒性无显著相关性。
Objective To investigate the association between methylenetetrahydrofolate reductase( MTHFR) rs1801131 A > C polymorphisms and clinical prognosis and toxicities of methotrexate( MTX) chemotherapy in children with acute lymphoblastic leukemia( ALL). Methods Peripheral blood samples were obtained from children with ALL( n = 134)to extract genome DNA. Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry( MALDI-TOF-MS) was used to detect the genotypes of MTHFR rs1801131 A > C polymorphisms. Results The average event free intervals( EFI) in children with MTHFR rs1801131 CC genotype( 26. 83 months) were significantly longer than those in AC genotype carriers( 15. 72 months,P < 0. 05). The relapse rate in patients with CC genotype( 0) was lower than those in AA( 9. 37%) and AC( 12. 50%) genotype carriers,but the differences were not statistically significant. The incidences of hepatic disorders and electrolyte disorders in children with CC genotype( 33. 33% and 16. 67%,respectively) were higher than those in AA( 12. 50% and 14. 58%) and AC( 18. 75% and 3. 13%) genotype carriers. The incidences of other adverse events in patients with CC genotype were lowerthan those in AA and AC genotype carriers. The differences in the incidences of MTX toxicities among three genotypes did not achieve statistical significance. Conclusion MTHFR rs1801131 A > C polymorphisms were significantly associated with clinical prognosis of ALL children. There were no significant associations between the investigated polymorphisms and toxicities of MTX.
引文
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