亚甲基四氢叶酸还原酶基因多态性与阿尔茨海默病的相关性临床研究

The clinical correlations of gene polymorphism of methylenetetrahydrofolate reductase with Alzheimer′s disease

目的探讨阿尔茨海默病(AD)进程中,亚甲基四氢叶酸还原酶(MTHFR)C677T多态性与疾病的相关性,以及是否受APOE基因影响。方法共纳入74例AD患者、85例遗忘型轻度认知障碍患者(aMCI)和81例健康对照者(HC),检测3组血清同型半胱氨酸(Hcy)、叶酸和维生素B12水平,以及MTHFR C677T及APOE基因型,通过Logistic回归分析比较MTHFR C677T不同等位基因和基因型分别与aMCI和AD风险之间的关联,以及在不同APOEε4亚组中的表现。结果AD组和aMCI组的血清Hcy水平均较对照组显著升高(P<0.001,P<0.001),而aMCI组血清叶酸水平较HC组明显降低(P=0.017)。与MTHFR CC、CT基因型者相比,TT基因型者的血清叶酸水平明显降低(P=0.038),血清Hcy水平明显升高(P=0.002)。回归分析结果显示:在APOEε4非携带者亚组中,MTHFR TT基因型可能增加aMCI患病风险(OR=3.670,95%CI=1.077-12.509,P=0.038),在APOEε4携带者中则无相应表现。结论MTHFR C677T多态性可导致血清Hcy水平增高和叶酸水平降低。在APOEε4非携带者中,MTHFR TT基因型可能增加aMCI的患病风险。

Objective To investigate the correlation between the methylenetetrahydrofolate reductase(MTHFR)C677T polymorphism and disease in the course of Alzheimer′s disease(AD),as well as whether whether it is affected by APOE gene.Methods A total of 74 AD patients,85 aMCI patients and 81 healthy controls(HC)were included.The levels of serum homocysteine(Hcy),folate,and vitamin B 12,as well as the genotypes of MTHFR C677T and APOE,were determined.Logistic regression analysis was conducted to explore the relationship between MTHFR C677T polymorphism and the risk of AD and aMCI,as well as in different APOEε4 subgroups.Results Compared with HC group,the serum Hcy levels in AD group and aMCI group were significantly higher(P<0.001,P<0.001),while serum folate levels in aMCI group was significantly lower(P=0.017).The serum folate level was significantly lower(P=0.038)in individuals with the MTHFR TT genotype compared to those with CC and CT genotypes,while the serum Hcy level was significantly higher(P=0.002).Regression analysis showed that the MTHFR TT genotype might increase the risk of aMCI in the subgroup of APOEε4 non-carriers(OR=3.670,95%CI=1.077-12.509,P=0.038),but not in APOEε4 carriers.Conclusion MTHFR C677T polymorphism plays an important role in Hcy metabolism,which leads to increased serum Hcy levels and decreased folate levels.In APOEε4 non-carriers,the MTHFR TT genotype may increase the risk of aMCI.