脊髓亚急性联合变性与MTHFR C677T基因多态性的相关性研究

The correlation between subacute combined degeneration of spinal cord and MTHFR C677T gene polymorphism

目的试图发现MTHFR基因多态性是导致脊髓亚急性联合变性(SCD)发病的遗传易感因素及其可能的机制,旨从遗传学角度进一步阐明SCD的发病机制,为SCD的早期诊断、治疗及预防供新的科学依据。方法研究采用病历-对照的研究方法,对两组患者的临床资料,包括年龄、性别、既往病史等进行分析比较;通过检测所有患者MTHFR C677T基因多态性、血清同型半胱氨酸(Hcy)浓度、维生素B_(12)水平等指标,并分别进行分析比较。结果①病历组的血清Hcy浓度(62.015μmol·L^(-1))明显高于对照组(16.910μmol·L^(-1))(P<0.001)。两组间大细胞性贫血病史及维生素B_(12)的缺乏率存在显著差异(P<0.001);而两组间叶酸浓度无统计学差异(P=1.000);②在病历组和对照组之间MTHFR C677T基因型多态性存在显著差异(P=0.015)。病历组中T等位基因出现频率显著高于对照组(70.2vs.52.6%),病历组中的C等位基因出现频率低于对照组(29.8%vs.47.4%)(P=0.003)。③在149例受试者中,将MTHFR C677T基因分为三组基因型,三组间血清Hcy浓度中位数上有统计学意义(H=27.205,P<0.001),经过两两对比,血浆Hcy浓度在CC组与TT组,CC组与CT组差异均有统计学意义(P<0.001)。但三组不同基因型在血清B_(12)和叶酸浓度上无统计学差异(P=0.439和P=0.773)。结论该研究结果表明,MTHFR 677TT基因多态性与中国人群中的SCD发病密切相关,可能是SCD的遗传易感因素;研究还表明,MTHFR 677TT基因突变可能通过降低5,10-亚甲基四氢叶酸还原酶活性,影响了Hcy向蛋氨酸的转化,从而影响了神经髓鞘的合成。因此,检测MTHFR C677T基因多态性对于SCD的早期诊断提供依据,为SCD的筛查、诊断及预防提供实验依据。

Objective This study attempts to explore that MTHFR gene polymorphism is the genetic susceptibility factor leading to subacute combined degeneration(SCD) and its possible mechanism,in order to further clarify the pathogenesis of SCD from the perspective of genetics,and provide new scientific basis for early diagnosis,treatment and prevention of SCD.Methods The clinical data of the two groups,including age,sex and past medical history were analyzed and compared by case-control study,and venous blood samples were taken to detect MTHFR C677 T gene polymorphism,serum Hey concentration,vitamin B_(12) level and so on.Results ① The serum Hey concentration in the case group(62.015 μmol·L^(-1)) was significantly higher than that in the control group(16.910μ mol·L^(-1))(P<0.001).There were significant differences in the history of large cell anemia and the rate of vitamin Bdeficiency between the two groups(P<0.001),but there was no significant difference in folic acid concentration between the two groups(P=1.000).② There was a significant difference in MTHFR C677 T genotype polymorphism between the case group and the control group(P=0.015).The frequency of T allele in the case group was significantly higher than that in the control group(70.2 vs.52.6%),while the frequency of C allele in the case group was lower than that in the control group(29.8 vs.47.4%)(P=0.003).③The MTHFR gene were divided into three genotypes in 149 subjects.There was significant difference in the median serum of the homocysteine concentration among the three groups(H=27.205,P<0.001).After pairwise comparison,there was significant difference in serum Hey concentration between CC and TT groups,and between CC and CT groups(P<0.001).However,there was no significant difference in serum Band folic acid concentrations among the three groups(P=0.439 and P=0.773).Conclusion The study shows that MTHFR 677 TT polymorphism is closely related to SCD in Chinese population and may be the genetic susceptibility factor of SCD,and the MTHFR 677 TT mutation may affects the transformation of homocysteine to methionine by reducing the activity of methylenetetrahydrofolate reductase,thus affecting the synthesis of nerve myelin sheath.Therefore,the detection of MTHFR C677 T gene polymorphism provides a basis for early diagnosis of SCD and theoretical basis for screening,diagnosis and prevention of SCD.