MTHFR基因多态性、Hcy与重性抑郁症的关联研究

Association of methylenetetrahydrofolate reductase gene polymorphism and plasma homocysteine with major depression

目的抑郁症是当前世界范围影响人类健康的常见病,患病率约为3%~5%。阐明其发病机理对抑郁症的治疗和预防有重要意义。目前对抑郁症的研究热点之一是MTHFR677C→T基因多态性与抑郁症的关系,但各家报道结果不一。本研究探讨中国北方汉族人群亚甲基四氢叶酸还原酶（methylene tetrahydrofolate reductase,MTHFR）基因多态性及血浆同型半胱氨酸（homocysteine,Hcy）水平与重性抑郁症的发病的相关性。方法采用病例对照研究,患者组156例,健康人对照组123例。用聚合酶链反应-限制性片段长度多态性分析技术（PCR-RFLP）检测MTHFR基因C677T多态性。循环酶法检测血浆Hcy水平。结果重性抑郁症组血浆Hcy水平较正常对照组显著增高,差异有显著性（P〈0.001）。重性抑郁症组MTH-FR677等位基因T过度表达,T纯合突变的基因频率增加,差异有显著性（P〈0.05）。患者组及健康人对照组677TT基因型者Hcy水平高于CC和CT基因型,差异有显著性（P〈0.05）。经Logistic回归分析MTHFR基因C677T的优势比为1.97,95%可信区间为[1.16,3.54]（P〈0.05）,血浆高Hcy的优势比为11.86,95%可信区间为[3.76,37.33]（P=0.003）。结论血浆Hcy水平增高及MTHFR基因C677T变异与重性抑郁症的发病有关,两者均为重性抑郁症的危险因素。

Objective Depression is a worldwide disease threatening human health and prevails in 3%-5% of the world population.An insight into the pathophysiology of this disorder is very important for its treatment and prevention.Many current researches focus on the relationship between MTHFR677C→T polymorphism and depression,but the results reported are controversial.This study was to explore the correlation of major depression with the level of plasma homocysteine（Hcy） and methylenetetrahydrofolate reductase（MTHFR） gene polymorphism in the Han population in northern China.Methods We included 156 depression patients and 123 healthy subjects in this case-control study,determined the MTHFR gene polymorphism by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）,and measured the plasma Hcy level by the cyclophorase method.Results Both the Hcy level and the homozygosity frequency of the 677T allele of the MTHFR gene were significantly increased in the patients in comparison with the controls（P0.001 and P0.05）.The plasma Hcy level was significantly higher in those with the TT genotype than in those with the CT or CC genotype（P0.05）.The logistic regression analysis showed that the MTHFRC677T genotype was associated with a higher risk of major depression,with an OR of 1.968（95% CI 1.16-3.54,P0.05）,and the OR for hyperhomocysteinemia was 11.86（95% CI 3.76-37.33,P=0.003）.Conclusion Both the elevated level of plasma Hcy and variation of the MTHFR677C→T gene are risk factors of major depression and associated with its increased incidence.