同型半胱氨酸代谢相关酶基因多态性与先天神经管缺陷的关系

Relationship between genetic polymorphism of homocysteine metabolism enzyme and congenital neural tube detects

目的:研究同型半胱氨酸相关酶中亚甲基四氢叶酸还原酶(MTHFR)及蛋氨酸合成酶还原酶(MTRR)基因的多态性与先天神经管缺陷的关系。方法:采用病例对照研究的方法,以64名先天神经管缺陷的胎儿及新生患儿(观察组)与104名无先天神经管缺陷的胎儿及新生儿(对照组)的血白细胞为样本,应用聚合酶链反应-限制性片段长度多态性技术检测两组的MTHFR基因第677位点及MTRR第66位点的多态性,比较两组各自的基因型和等位基因的分布频率。结果:MTHFR的677位点CC、CT和TT基因型在疾病组中分别为26.56%、45.31%、28.13%,在对照组中分别为43.27%、44.23%、12.50%。两组的分布频率差异有显著性。MTRR基因第66位点AA、AG和GG基因型在疾病组分别为15.63%、70.31%、14.06%,在对照组中分别为48.08%、43.27%、8.65%。两组的分布频率差异有显著性。结论:①MTHFR基因第677位点及MTRR第66位点的多态性与先天神经管缺陷的发病具有一定程度的相关性;②MTHFR基因第677位点中的C/C及MTRR第66位点中的A/A均为先天神经管缺陷的保护基因;③两基因变异在先天神经管缺陷的发病中可能有协同作用。

Objective： To detect the distribution of polymorphism of MTHFR gene and MTRR gene in fetus or neonatal with congenital neural tube detects （disease group） and normal controls. Methods： Polymorphism of the 677th site C/T of MTHFR gene and the 66th site A/G of MTRR gene were detected by polymemse chain reaction - restretion fragment length polymorphism in disease group （ n = 64） and normal controls （n = 104） . Results： To the 677th site of MTHFR gene the frequencies of CC, CT and TT genotypes were 26.56%, 45.31% and 28. 13% in disease group, while 43.27%, 44. 23% and 12. 50% in normal controls. A significant difference was seen in the distribution frequency in two groups; To the 66th site of MTRR gene the frequencies of AA, AG and GG genotypes were 15.63% , 70. 31% and 14. 06% in disease group, while 48.08%, 43.27% and 8.65% in normal controls. A significant difference was seen in the distribution frequency in two groups. Conclusion： The distribution frequency of MTHFR gene and MTRR gene have something to do with morhility of congenital neural tube detects; genotypes C/C in MTHFR gene and A/A in MTRR gene may have a protective effect against congenital neural tube detects; There may exist some interaction between polymorphisms of MTHFR gene MTRR gene in the pathogenesis of congenital neural tube detects.