叶酸和核黄素缺乏对不同MTHFR C677T基因型个体染色体分离的影响

THE IMPACTS OF VARIATION OF FOLATE METABOLIC COMPONENT AND MTHFR C677T POLYMORPHISMS ON CHROMOSOME SEGREGATION

目的探讨叶酸(FA)缺乏、叶酸代谢核心酶亚甲基四氢叶酸还原酶基因MTHFRC677T多态性和MTHFR辅酶前体核黄素(RF)缺乏,对人类淋巴细胞8号和17号染色体分离的影响。方法以低(LF)和高(HF)浓度叶酸(20、200nmol/L)和核黄素低(LR)高(HR)浓度(1、500nmol/L)组合的RPMI1640培养基培养不同MTHFRC677T基因型的人类淋巴细胞,细胞松弛素B阻滞细胞质分裂后制片,以多色荧光原位杂交法分析8号和17号染色体非整倍体。结果受试染色体非整倍体频率在HFHR和HFLR培养条件下即高叶酸都显著低于低叶酸的两种培养条件(LFLR和LFHR)(P<0.001),而不同的核黄素培养条件即高水平(HFHR和LFHR)与低水平(HFLR和LFLR)间无诱发非整倍体频率的显著差异;MTHFRC677T各基因型间亦未发现染色体异常分离的显著差异。结论叶酸是维持染色体正常分离的主导因素,研究提示核黄素和MTHFRC677T多态性对受试染色体分离没有显著影响。

Objective To study the impacts of variation of folate metabolic component including folic acid （FA）, riboflavin （RF） and MTHFR C677T polymorphism on chromosome 8 and 17 segregation. Method RPMI1640 medium was modified with different combinations of low （LF） and high （HF） concentrations of folic acid （20, 200 nmol/L） and low （LR） and high （HR） concentrations of riboflavin （1 and 500 nmol/L）. The lymphocytes with different MTFHR C677T genotype were cultured in the mentioned media for 9d. Cytokinesis was blocked by cytochalasin B and the slide was prepared as usual. The frequencies of aneuploidy of chromosomes 8 and 17 were determined by dual-color fluorescence in situ hybridization （FISH）. Results The frequencies of both chromosome aneuploidy were significantly higher in low FA （LFLR＋LFHR） than that in higher FA （HFLR＋HFHR） （P〈0.001）. No significant difference in the aneuploidy induction effect by different combinations of high and low riboflavin. There is no significant impact on aneuploidy induction by MTHFR C677T polymorphism. Conclusion Folic acid is the dominant factor that protect chromosome 8 and 17 from malsegregation.